Covid-19 interface with drug misuse and substance use disorders.

The coronavirus disease 2019 (Covid-19) pandemic intensified the already catastrophic drug overdose and substance use disorder (SUD) epidemic, signaling a syndemic as social isolation, economic and mental health distress, and disrupted treatment services disproportionally impacted this vulnerable population. Along with these social and societal factors, biological factors triggered by intense stress intertwined with incumbent overactivity of the immune system and the resulting inflammatory outcomes may impact the functional status of the central nervous system (CNS). We review the literature concerning SARS-CoV2 infiltration and infection in the CNS and the prospects of synergy between stress, inflammation, and kynurenine pathway function during illness and recovery from Covid-19. Taken together, inflammation and neuroimmune signaling, a consequence of Covid-19 infection, may dysregulate critical pathways and underlie maladaptive changes in the CNS, to exacerbate the development of neuropsychiatric symptoms and in the vulnerability to develop SUD. This article is part of the special Issue on 'Vulnerabilities to Substance Abuse'.

Loneliness and quality of life after head and neck cancer.

Loneliness is associated with a poor quality of life, mental illness, poor physical health, and premature mortality. Patients with head and neck cancer (HNC) are at risk of loneliness because of the effects of the disease and its treatment on important social interactive functions such as appearance, speech, facial expression, and eating. Patients treated for primary squamous cell HNC between January 2015 and December 2016 were surveyed in early 2019 using the University of Washington quality of life questionnaire version 4, the Cancer-related Loneliness Assessment Tool (C-LAT), and four nationally recommended indicator questions. The survey comprised 140 patients, with a mean (standard deviation) age at diagnosis of 63 (11) years. Tumour sites were oropharyngeal (42%), oral (35%), laryngeal (14%), and elsewhere (9%). In response to the question "How often do you feel lonely?" three-quarters said "hardly ever" and only 6% "often". Similar responses were obtained for the other three indicator questions. It is encouraging that a relatively small proportion had serious issues with loneliness. Similarly, responses to the C-LAT suggested that one-quarter had feelings of loneliness and a minority had serious problems. Patients who were younger, who lived in more deprived circumstances, who had advanced disease and had been treated with chemotherapy or radiotherapy reported greater levels of loneliness. Loneliness was associated with a worse overall quality of life, and worse physical and social-emotional function. Lonely patients need to be identified as early as possible so that support and interventions can be implemented and outcomes improved.

Effect of a Nurse-Led Protocol on Time to Treatment of Partial Occlusions in Central Venous Access Devices in Pediatric Oncology.

Central venous access devices (CVADs) are the standard of care in pediatric oncology. Occlusion is a common complication that can lead to delays in therapy, readmission, and CVAD removal and reinsertion. Early treatment of partial occlusions using a standardized protocol may restore patency and increase life span of CVADs. The objective of this study was to develop and evaluate a nurse-led protocol to manage partial CVAD occlusions in pediatric oncology and autologous bone marrow transplant patients. The protocol enabled nurses to manage partially occluded CVADs by administering thrombolytic therapy following an algorithm and patient-specific standing order. The primary outcome was time from recognition of the partial occlusion to instillation of a thrombolytic. Secondary outcomes were thrombolytic dwell time, number of complete occlusions, and CVAD life span. We used a quasi-experimental, after-only, nonequivalent control group design to compare patients not exposed (retrospective cohort, n = 137) and patients exposed (prospective cohort, n = 101) to the nurse-led protocol. Mann-Whitney U tests were used to compare time to treatment, dwell time, and CVAD life span between cohorts, and χ2 was used to compare the proportion of occlusions classified as complete. Time to treatment was significantly lower in the prospective cohort (M = 99.9 minutes) versus the retrospective cohort (M = 483.7 minutes), U = 1366.50, p < .01, as was thrombolytic dwell time, U = 282.50, p < .01. Proportion of complete occlusions and CVAD life span did not differ between cohorts. The nurse-led protocol was effective to manage partial CVAD occlusions in pediatric oncology patients.

Point of Care Ultrasound in the Diagnosis and Management of Severe Ovarian Hyperstimulation Syndrome.

Presentation A 32year old woman, presented with a 5-day history of non-productive cough, chest pain, shortness of breath andabdominal bloating. She had undergone Embryo Transfer Treatment 6 days previously. Diagnosis A point of care ultrasound (POCUS) exam was performed as part of her initial investigations which showed right pleuraleffusion, ascites and cystic ovaries. Treatment She received Oxygen, IV Fluids and Antibiotics and was referred to the Obstetricians. Discussion Point of care ultrasound (POCUS) aided the prompt diagnosis of ovarian hyperstimulation syndrome (OHSS) in thispatient, making it possible for her to receive appropriate resuscitation and referral and an excellent outcome despitethis being a case of severe ovarian hyperstimulation syndrome.

Development of the cancer-related loneliness assessment tool: Using the findings of a qualitative analysis to generate questionnaire items.

The aim of this research was to develop a tool to identify and assess the qualities of cancer-related loneliness in adult cancer survivors who have completed treatment. In addition to reporting the development of the tool, we explicate the process of using the findings of a qualitative analysis to generate questionnaire items, as currently little guidance exists on this topic. The findings of our qualitative research exploring the experience of loneliness in adult cancer survivors who had completed treatment, together with the findings of our concept analysis of loneliness, were used to develop an assessment tool for cancer-related loneliness following treatment completion. Cognitive testing was undertaken to assess fidelity of comprehension and feasibility in administration. The Cancer-Related Loneliness Assessment Tool is a 10-item self-report questionnaire capturing the essential elements of cancer-related loneliness following treatment completion. Experts believed the questionnaire to be face-valid and usable in clinical practice, and preliminary cognitive testing indicated that the items generate the information intended and individuals have little trouble completing the tool. Following further development work, the tool could be employed to identify cancer-related loneliness following treatment completion. It could also aid with the development/adaptation and evaluation of person-centred interventions to address such loneliness.

Incubation of cocaine cue reactivity associates with neuroadaptations in the cortical serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system.

Intensification of craving elicited by drug-associated cues during abstinence occurs over time in human cocaine users while elevation of cue reactivity ("incubation") is observed in rats exposed to extended forced abstinence from cocaine self-administration. Incubation in rodents has been linked to time-dependent neuronal plasticity in the medial prefrontal cortex (mPFC). We tested the hypothesis that incubation of cue reactivity during abstinence from cocaine self-administration is accompanied by lower potency and/or efficacy of the selective serotonin (5-HT) 5-HT2C​ receptor (5-HT2CR) agonist WAY163909 to suppress cue reactivity and a shift in the subcellular localization profile of the mPFC 5-HT2CR protein. We observed incubation of cue reactivity (measured as lever presses reinforced by the discrete cue complex) between Day 1 and Day 30 of forced abstinence from cocaine relative to sucrose self-administration. Pharmacological and biochemical analyses revealed that the potency of the selective 5-HT2CR agonist WAY163909 to suppress cue reactivity, the expression of synaptosomal 5-HT2CR protein in the mPFC, and the membrane to cytoplasmic expression of the 5-HT2CR in mPFC were lower on Day 30 vs. Day 1 of forced abstinence from cocaine self-administration. Incubation of cue reactivity assessed during forced abstinence from sucrose self-administration did not associate with 5-HT2CR protein expression in the mPFC. Collectively, these outcomes are the first indication that neuroadaptations in the 5-HT2CR system may contribute to incubation of cocaine cue reactivity.

The recurrence risk of placenta accreta following uterine conserving management.

BACKGROUND: Placenta accreta is a condition of abnormal placental attachment that was usually treated by hysterectomy. Techniques to conserve the uterus are now commonly used and series of subsequent pregnancy outcomes have been reported. The recurrence risk of placenta accreta is now a relevant detail and is currently not known. This work was performed to calculate the recurrence risk by reviewing the published literature. METHODS: A literature search using the terms "placenta accreta", "placenta percreta", "placenta increta", "abnormal placental attachment" and "placental attachment disorder" followed by hand-searching identified 6 papers that contained data concerning recurrence of placenta accreta in subsequent pregnancies following initial conservative treatment. RESULTS: Overall 407 pregnancies were recorded and 85.7% of women reported achieved a subsequent pregnancy following conservative treatment. The risk of recurrence of placental attachment disorder in a subsequent pregnancy was 19.9% (weighted mean, 95% CI 12.2-27.7). CONCLUSIONS: The recurrence risk of placental attachment disorder following uterine conservation treatments is 20% . This risk should be discussed with women with an antenatal diagnosis of a placental attachment disorder who may be considering uterine conservation in order to retain the option of a future pregnancy.

A cross-sectional study of tetanus and diphtheria antibody concentrations post vaccination among lung transplant patients compared with healthy individuals.

BACKGROUND: Lung transplant (LuTx) patients are routinely immunized against tetanus and diphtheria. However, few studies have been done to measure serologic immunity in the transplant population. OBJECTIVES: The primary objective of this study was to compare tetanus and diphtheria antibody concentrations in LuTx vs. healthy subjects. METHODS: Serum was used from an available sample of 111 total individuals (n = 36 healthy; n = 75 LuTx). Tetanus and diphtheria antibody concentrations were measured using an enzyme-linked immunosorbant assay method. RESULTS: A statistically significant difference in both tetanus and diphtheria antibody concentrations was found between the groups. The median concentration of tetanus antibody was higher for healthy individuals compared with the LuTx group (3.2 IU/mL [1.2-5.2 interquartile range {IQR}] vs. 1.3 IU/mL [0.4-2.6 IQR], respectively; P = 0.0001). No difference in time was found since the last tetanus-diphtheria vaccine or tetanus-diphtheria-pertussis vaccine dose between the groups (healthy 76.5 months [16-114 IQR] vs. LuTx 74.5 months [45-118 IQR]; P = 0.44). CONCLUSIONS: Tetanus and diphtheria immunizations are recommended for LuTx patients to reduce the risk of infection. Because the LuTx group has lower antibody concentrations, further studies should investigate the possible need for more frequent tetanus and diphtheria boosters.

Infants with FPIES to solid food proteins--chicken, rice and oats.

We present two cases of Food Protein Induced Enterocolitis Syndrome (FPIES), a non-IgE mediated food hypersensitivity. FPIES induces severe vomiting 1.5-to-3 hours post ingestion of the offending food, and may be associated with diarrhoea, hypovolemic shock and acidosis. Avoidance of that food will lead to resolution of symptoms and prevents further episodes.

Variation within the serotonin (5-HT) 5-HT2C receptor system aligns with vulnerability to cocaine cue reactivity.

Cocaine dependence remains a challenging public health problem with relapse cited as a major determinant in its chronicity and severity. Environmental contexts and stimuli become reliably associated with its use leading to durable conditioned responses ('cue reactivity') that can predict relapse as well as treatment success. Individual variation in the magnitude and influence of cue reactivity over behavior in humans and animals suggest that cue-reactive individuals may be at greater risk for the progression to addiction and/or relapse. In the present translational study, we investigated the contribution of variation in the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system in individual differences in cocaine cue reactivity in humans and rodents. We found that cocaine-dependent subjects carrying a single nucleotide polymorphism (SNP) in the HTR2C gene that encodes for the conversion of cysteine to serine at codon 23 (Ser23 variant) exhibited significantly higher attentional bias to cocaine cues in the cocaine-word Stroop task than those carrying the Cys23 variant. In a model of individual differences in cocaine cue reactivity in rats, we identified that high cocaine cue reactivity measured as appetitive approach behavior (lever presses reinforced by the discrete cue complex) correlated with lower 5-HT2CR protein expression in the medial prefrontal cortex and blunted sensitivity to the suppressive effects of the selective 5-HT2CR agonist WAY163909. Our translational findings suggest that the functional status of the 5-HT2CR system is a mechanistic factor in the generation of vulnerability to cocaine-associated cues, an observation that opens new avenues for future development of biomarker and therapeutic approaches to suppress relapse in cocaine dependence.

Ovarian steroid hormones: effects on immune responses and Chlamydia trachomatis infections of the female genital tract.

Female sex hormones are known to regulate the adaptive and innate immune functions of the female reproductive tract. This review aims to update our current knowledge of the effects of the sex hormones estradiol and progesterone in the female reproductive tract on innate immunity, antigen presentation, specific immune responses, antibody secretion, genital tract infections caused by Chlamydia trachomatis, and vaccine-induced immunity.

Potential benefits of satiety to the consumer: scientific considerations.

Foods and dietary patterns that enhance satiety may provide benefit to consumers. The aim of the present review was to describe, consider and evaluate research on potential benefits of enhanced satiety. The proposal that enhanced satiety could only benefit consumers by a direct effect on food intake should be rejected. Instead, it is proposed that there is a variety of routes through which enhanced satiety could (indirectly) benefit dietary control or weight-management goals. The review highlights specific potential benefits of satiety, including: providing appetite control strategies for consumers generally and for those who are highly responsive to food cues; offering pleasure and satisfaction associated with low-energy/healthier versions of foods without feeling 'deprived'; reducing dysphoric mood associated with hunger especially during energy restriction; and improved compliance with healthy eating or weight-management efforts. There is convincing evidence of short-term satiety benefits, but only probable evidence for longer-term benefits to hunger management, possible evidence of benefits to mood and cognition, inadequate evidence that satiety enhancement can promote weight loss, and no evidence on which consumers would benefit most from satiety enhancement. The appetite-reducing effects of specific foods or diets will be much more subtle than those of pharmaceutical compounds in managing hunger; nevertheless, the experience of pharmacology in producing weight loss via effects on appetite suggests that there is potential benefit of satiety enhancement from foods incorporated into the diet to the consumer.

STEPS: lean thinking, theory of constraints and identifying bottlenecks in an emergency department.

This study aimed to identify the bottlenecks in patients' journeys through an emergency department (ED). For each stage of the patient journey, the average times were compared between two groups divided according to the four hour time frame and disproportionate delays were identified using a significance test These bottlenecks were evaluated with reference to a lean thinking value-stream map and the five focusing steps of the theory of constraints. A total of 434 (72.5%) ED patients were tracked over one week. Logistic regression showed that patients who had radiological tests, blood tests or who were admitted were 4.4, 4.1 and 7.7 times more likely, respectively, to stay over four hours in the ED than those who didn't The stages that were significantly delayed were the time spent waiting for radiology (p = 0.001), waiting for the in-patient team (p = 0.004), waiting for a bed (p < 0.001) and ED doctor turnaround time (p < 0.001).

Stem cell collection in patients with multiple myeloma: impact of induction therapy and mobilization regimen.

Lenalidomide is an active treatment for multiple myeloma (MM) and is increasingly used as part of the initial treatment of this disease. Recent reports have suggested decreases in the number of CD34+ cells collected and increases in the failure rate among patients whose initial therapy contained lenalidomide when mobilized with G-CSF alone. A retrospective data analysis of 364 patients with MM who underwent stem cell mobilization and attempted harvest at the Hospital of the University of Pennsylvania between January 2002 and December 2007 was performed. Forty-three of the patients received lenalidomide in their induction regimen, and were mobilized with either CY and G-CSF or G-CSF alone. The number of apheresis cycles and the failure rate were lower, whereas the mean number of collected stem cells was higher in patients who were mobilized with CY and G-CSF in comparison with G-CSF alone. This suggests that lenalidomide does not prevent the harvest of adequate numbers of CD34 cells for autologous stem cell transplant, but mobilization with G-CSF and CY may be required to obtain adequate numbers of stem cells. Finally, in our study, the number of lenalidomide cycles did not correlate with stem cell yield.

Gastrointestinal targets of appetite regulation in humans.

The aim of this paper is to describe and discuss relevant aspects of the assessment of physiological functions - and related biomarkers - implicated in the regulation of appetite in humans. A short introduction provides the background and the present state of biomarker research as related to satiety and appetite. The main focus of the paper is on the gastrointestinal tract and its functions and biomarkers related to appetite for which sufficient data are available in human studies. The first section describes how gastric emptying, stomach distension and gut motility influence appetite; the second part describes how selected gastrointestinal peptides are involved in the control of satiety and appetite (ghrelin, cholecystokinin, glucagon-like peptide, peptide tyrosin-tyrosin) and can be used as potential biomarkers. For both sections, methodological aspects (adequacy, accuracy and limitation of the methods) are described. The last section focuses on new developments in techniques and methods for the assessment of physiological targets involved in appetite regulation (including brain imaging, interesting new experimental approaches, targets and markers). The conclusion estimates the relevance of selected biomarkers as representative markers of appetite regulation, in view of the current state of the art.

3D strain measurement in soft tissue: demonstration of a novel inverse finite element model algorithm on MicroCT images of a tissue phantom exposed to negative pressure wound therapy.

This study describes a novel system for acquiring the 3D strain field in soft tissue at sub-millimeter spatial resolution during negative pressure wound therapy (NPWT). Recent research in advanced wound treatment modalities theorizes that microdeformations induced by the application of sub-atmospheric (negative) pressure through V.A.C. GranuFoam Dressing, a reticulated open-cell polyurethane foam (ROCF), is instrumental in regulating the mechanobiology of granulation tissue formation [Saxena, V., Hwang, C.W., Huang, S., Eichbaum, Q., Ingber, D., Orgill, D.P., 2004. Vacuum-assisted closure: Microdeformations of wounds and cell proliferation. Plast. Reconstr. Surg. 114, 1086-1096]. While the clinical response is unequivocal, measurement of deformations at the wound-dressing interface has not been possible due to the inaccessibility of the wound tissue beneath the sealed dressing. Here we describe the development of a bench-test wound model for microcomputed tomography (microCT) imaging of deformation induced by NPWT and an algorithm set for quantifying the 3D strain field at sub-millimeter resolution. Microdeformations induced in the tissue phantom revealed average tensile strains of 18%-23% at sub-atmospheric pressures of -50 to -200 mmHg (-6.7 to -26.7 kPa). The compressive strains (22%-24%) and shear strains (20%-23%) correlate with 2D FEM studies of microdeformational wound therapy in the reference cited above. We anticipate that strain signals quantified using this system can then be used in future research aimed at correlating the effects of mechanical loading on the phenotypic expression of dermal fibroblasts in acute and chronic ulcer models. Furthermore, the method developed here can be applied to continuum deformation analysis in other contexts, such as 3D cell culture via confocal microscopy, full scale CT and MRI imaging, and in machine vision.

Blockade of the serotonin 5-HT2A receptor suppresses cue-evoked reinstatement of cocaine-seeking behavior in a rat self-administration model.

The serotonin 5-HT2A receptor (5-HT-sub(2A)R) may play a role in reinstatement of drug-seeking. This study investigated the ability of a selective 5-HT-sub(2A)R antagonist to suppress reinstatement evoked by exposure to cues conditioned to cocaine self-administration. Cocaine self-administration (0.75 mg/kg/0.1 mL/6 s infusion; FR 4) was trained in naïve, free-fed rats to allow interpretation of results independent from changes related to food deprivation stress. Pretreatment with the selective 5-HT-sub(2A)R antagonist M100907 (volinanserin) failed to reduce rates of operant responding for cocaine infusions. On the other hand, M100907 (0.001-0.8 mg/kg ip) significantly suppressed the cue-induced reinstatement of cocaine-seeking behavior following extinction; effective M100907 doses did not alter operant responding for cues previously associated with sucrose self-administration. Importantly, a greater magnitude of active lever presses on the initial extinction session (high extinction responders) predicted the maximal susceptibility to M100907-induced suppression of cue-evoked reinstatement. The findings indicate that blockade of the 5-HT-sub(2A)R attenuates the incentive-motivational effects of cocaine-paired cues, particularly in high extinction responders, and suggests that M100907 may afford a therapeutic advance in suppression of cue-evoked craving and/or relapse.