Impact of Covid-19 on farming systems in Europe through the lens of resilience thinking.

Context: Resilience is the ability to deal with shocks and stresses, including the unknown and previously unimaginable, such as the Covid-19 crisis. Objective: This paper assesses (i) how different farming systems were exposed to the crisis, (ii) which resilience capacities were revealed and (iii) how resilience was enabled or constrained by the farming systems' social and institutional environment. Methods: The 11 farming systems included have been analysed since 2017. This allows a comparison of pre-Covid-19 findings and the Covid-19 crisis. Pre-Covid findings are from the SURE-Farm systematic sustainability and resilience assessment. For Covid-19 a special data collection was carried out during the early stage of lockdowns. Results and conclusions: Our case studies found limited impact of Covid-19 on the production and delivery of food and other agricultural products. This was due to either little exposure or the agile activation of robustness capacities of the farming systems in combination with an enabling institutional environment. Revealed capacities were mainly based on already existing connectedness among farmers and more broadly in value chains. Across cases, the experience of the crisis triggered reflexivity about the operation of the farming systems. Recurring topics were the need for shorter chains, more fairness towards farmers, and less dependence on migrant workers. However, actors in the farming systems and the enabling environment generally focused on the immediate issues and gave little real consideration to long-term implications and challenges. Hence, adaptive or transformative capacities were much less on display than coping capacities. The comparison with pre-Covid findings mostly showed similarities. If challenges, such as shortage of labour, already loomed before, they persisted during the crisis. Furthermore, the eminent role of resilience attributes was confirmed. In cases with high connectedness and diversity we found that these system characteristics contributed significantly to dealing with the crisis. Also the focus on coping capacities was already visible before the crisis. We are not sure yet whether the focus on short-term robustness just reflects the higher visibility and urgency of shocks compared to slow processes that undermine or threaten important system functions, or whether they betray an imbalance in resilience capacities at the expense of adaptability and transformability. Significance: Our analysis indicates that if transformations are required, e.g. to respond to concerns about transnational value chains and future pandemics from zoonosis, the transformative capacity of many farming systems needs to be actively enhanced through an enabling environment.

Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: Armodafinil is the R-enantiomer of racemic modafinil and has a significantly longer half-life than the S-enantiomer. This study evaluated armodafinil 150 mg/day as an adjunct treatment for residual excessive sleepiness in patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) who were otherwise well controlled with nasal continuous positive airway pressure (nCPAP). We assessed the ability of armodafinil to improve wakefulness and cognition and reduce fatigue in this population. METHODS: In this 12-week, randomized, double-blind study, patients (n=259) received armodafinil (150 mg) or placebo once daily. Efficacy assessments at baseline and weeks 4, 8, and 12 included the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Change (CGI-C), Cognitive Drug Research battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory. RESULTS: At final visit, mean (SD) MWT sleep latency increased from baseline by 2.3 (7.8) min with armodafinil and decreased by 1.3 (7.1) min in the placebo group (P=0.0003). Armodafinil improved clinical condition (CGI-C, 71% vs. 53% for armodafinil and placebo, respectively; P=0.0069). Armodafinil significantly improved episodic secondary memory (P=0.0102) and patient-estimated wakefulness (P<0.01) and reduced fatigue (P<0.05) compared with placebo. Armodafinil did not adversely affect nCPAP use. The most common adverse event associated with armodafinil was headache. Sleep macroarchitecture was not altered by armodafinil. CONCLUSION: Adjunct treatment with armodafinil significantly improved alertness, overall clinical condition, and long-term memory. Armodafinil also reduced fatigue and the impact of sleepiness on daily activities in patients with OSA/HS who have residual excessive sleepiness notwithstanding regular use of nCPAP. Armodafinil was well tolerated.

Matrix Metalloproteinases -14, -9 and -2 are Localized to the Podosome and Involved in Podosome Development in the A7r5 Smooth Muscle Cell.

AIM: The purpose of the study was to localize matrix metalloproteinase (MMP)-14, -9, and -2 in the A7r5 smooth muscle cell and to understand the interaction between these MMPs and the cytoskeleton. This interaction was observed under non-stimulating and phorbol 12, 13-dibutyrate (PDBu)-stimulating conditions. METHODS: Confocal microscopy was utilized to define the localizations of MMPs and tissue inhibitor of matrix metalloproteinases (TIMPs) in the A7r5 cell and to determine interaction between MMPs and the cytoskeleton. Under PDBu-stimulating conditions, the presence of MMP active forms and activity by gel zymography was evaluated in the A7r5 cell. Actin and microtubule-polymerization inhibitors were used to evaluate MMP interaction with the cytoskeleton and the cytoskeleton was observed on matrix and within a Type I collagen gel. RESULTS: MMP-14, -9, and -2 were localized to the podosome in the A7r5 smooth muscle cell and interactions were seen with these MMPs and the actin cytoskeleton. PDBu-stimulation induced increases in the protein abundance of the active forms of the MMPs and MMP-2 activity was increased. MMPs also interact with a-actin and not ß-tubulin in the A7r5 cell. Galardin, also known as GM-6001, was shown to inhibit podosome formation and prevented MMP localization to the podosome. This broad spectrum MMP inhibitor also prevented collagen gel contraction and prevented cell adhesion and spreading of A7r5 cells within this collagen matrix. CONCLUSION: MMPs are important in the formation and function of podosomes in the A7r5 smooth muscle cell. MMPs interact with a-actin and not ß-tubulin in the A7r5 cell. Podosomes play an important role in cell migration and understanding the function of podosomes can lead to insights into cancer metastasis and cardiovascular disease.

Noradrenergic dysregulation during discontinuation of cocaine use in addicts.

BACKGROUND: The primary objective of the study was to prospectively determine possible noradrenergic dysregulation in cocaine addicts by assessing biochemical, behavioral, and cardiovascular responses to intravenous yohimbine hydrochloride during early and late discontinuation of cocaine use. METHODS: Twelve male and two female hospitalized cocaine-dependent subjects (mean +/- SD age, 30.9 +/- 7.3 years) who were not seeking primary treatment for addiction participated voluntarily for monetary remuneration. Following an initial test dose of intranasal cocaine, 2 mg/kg, cocaine addicts received single-blind, monitored cocaine insufflation, 2 mg/kg three times each day, for 3 consecutive days. One to two days (early discontinuation) and 15 to 16 days (late discontinuation) after the last dose of cocaine, subjects received double-blind, randomized intravenous infusions of yohimbine hydrochloride, 0.4 mg/kg, or placebo. Plasma 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and plasma cortisol levels, anxiety-related symptoms on clinician- and subject-rated scales, blood pressure, and heart rate were measured throughout each test day. Ten of 14 subjects completed the entire study. RESULTS: Subjects had a significantly greater placebo-corrected MHPG response to yohimbine during early compared with late discontinuation. Subjects rated themselves significantly more nervous following yohimbine administration during early compared with late discontinuation. Seventy-one percent of subjects experienced a yohimbine-induced panic attack during early discontinuation compared with none during late discontinuation. CONCLUSIONS: The results of this study provide evidence of an underlying dysregulation in noradrenergic function and a vulnerability to panic anxiety during early discontinuation of cocaine use in addicts. Additional investigations of noradrenergic function appear warranted to further clarify derangements associated with cocaine addiction.

Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning.

This study compared the morphology of cerebellar cortex in adult female rats exposed for 1 month to repetitive exercise, motor learning, or an inactive condition. In the exercise conditions, rats that were run on a treadmill or housed with access to a running wheel had a shorter diffusion distance from blood vessels in the molecular layer of the paramedian lobule when compared to rats housed individually or rats that participated in a motor skill learning task. Rats taught complex motor skills substantially increased the volume of the molecular layer per Purkinje neuron and increased blood vessel number sufficiently to maintain the diffusion distance. These results dissociate angiogenesis associated with increased neuropil volume (as seen in the motor learning group) from angiogenesis associated with increased metabolic demands (as seen in the exercise groups). While the volume fraction of mitochondria did not differ among groups, the mitochondrial volume fraction per Purkinje cell was significantly increased in the motor skill rats. This appears to parallel the previously reported increase in synapses and associated neuropil volume change.

Progressive failure of cerebral angiogenesis supporting neural plasticity in aging rats.

Previous work has demonstrated substantial formation of new synapses and capillary branches in visual cortex of young rats provided with complex experience. Synaptogenesis appears greatly weakened in old rats, however, perhaps because of an age-associated impairment of metabolic support. We have examined capillaries in visual cortex from eight 14-month-old and nine 24-month-old rats that had been kept for 50 days in either a complex environment with toys and other rats or in the standard laboratory condition they had been raised in. In spite of tissue expansion that increased cortical thickness and spread apart existing blood vessels in 14-month-old rats that received complex experience, the density of capillaries was not affected. These results indicate that new capillaries infiltrated the expanding tissue. These rats also had significantly more small-diameter capillaries, possibly reflecting the immaturity of new vessels and effectively reducing the maximum amount of blood available to the tissue. Similar but nonsignificant trends were observed in the 24-month-old animals given complex experience. These results suggest that angiogenesis, while it does occur, is substantially impaired in middle-aged animals, and a failure of angiogenesis in old rats may explain their reduced capacity for synaptogenesis.

Usual vs. successful aging: some notes on experiential factors.

A common analogy to aging is that of a boulder being worn down to rubble by the unremitting onslaught of time. In contrast, Swaab's "use it or lose it" concept is important because it emphasizes some positive consequences of experience. For example, early exposure to complex experience may offer some protection from "wear and tear" degradation through improvements in vascular support, diet, exercise, and coping with stress. Exposure to complex experience in old age can also generate new synapses in the cerebral cortex and cerebellum. This new perspective is not completely positive, however, because it appears that the senescent breakdown of supporting systems may ultimately constrain the positive benefits of experience in old age. Thus the evidence indicates that the use of environmental therapies should encompass the entire life span to produce successful aging.

Serotonergic mechanisms of cocaine effects in humans.

The objective of this study was to investigate the role of serotonin (5-HT) in mediating the effects of cocaine in humans. To accomplish this, 12 subjects each participated in two randomized, double-blind test sessions separated by 1 week. In one session, subjects underwent acute depletion of the 5-HT amino acid precursor tryptophan (TRP), followed by a test dose of intranasal cocaine. In the other session, the cocaine test dose was preceded by sham depletion. Subject ratings of cocaine "high" were significantly lower following active TRP depletion than after the sham procedure. Subjects also showed an earlier but less sustained rise in self-rated nervousness during active TRP depletion. These findings are consistent with the hypothesis that 5-HT may be involved in mediating the euphorigenic and modulating the anxiogenic effects of cocaine in humans, either directly or through actions on other (e.g., dopaminergic) systems.

Concurrent cocaine-ethanol ingestion in humans: pharmacology, physiology, behavior, and the role of cocaethylene.

Simultaneous abuse of cocaine and ethanol is a common occurrence. Cocaethylene, the ethyl ester of benzoylecgonine, has been detected in the urine of patients reporting concurrent use of cocaine and ethanol, and high levels have been found in the blood of victims of fatal drug overdose. This placebo-controlled, double-blind study examined the pharmacokinetic, physiologic, and behavioral effects of dual cocaine and ethanol administration in humans (n = 6). Cocaethylene was found in the plasma only after administration of both cocaine and ethanol, and appeared to be eliminated more slowly than cocaine. Plasma cocaine concentrations were significantly higher during cocaine/ethanol administration. Euphorigenic effects were both enhanced and prolonged, and heart rate was significantly increased, following cocaine/ethanol administration as compared to administration of cocaine or ethanol alone.

Direct evidence that complex experience increases capillary branching and surface area in visual cortex of young rats.

Rats housed in complex environments with toys and other rats generate new synapses, and the expanding neuropil tends to spread apart existing blood vessels. Previous work demonstrated that weanling rats kept in complex environments had more closely packed capillaries, suggesting that new capillaries had sprouted into the newly added neuropil. The present study directly investigates the issue of new branching by using india ink perfusions of weanling rats kept for 30 days in a complex environment (EC), paired in standard caging (SC), or individual cages (IC) to examine the density of capillary branch points and the capillary surface area per unit tissue volume. EC rats had a greater density of branch points than the SC and IC littermates, a finding consistent with increased capillary sprouting. Capillary surface area per unit tissue volume and the number of branch points per unit of capillary surface area were also higher for EC rats. This suggests that blood vessels of EC rats branch off more often than those of animals kept in more standard conditions, and provides further evidence that complex experience can increase angiogenesis in cerebral cortex of postweanling rats.

Complex experience promotes capillary formation in young rat visual cortex.

The metabolic support of neural plasticity was examined by comparing cerebral vasculature of weanling rats reared in complex environments (EC) to littermates reared individually (IC) or socially in pairs (SC). EC rats have a thicker occipital cortex, more synaptic contacts per neuron and larger dendritic arbors compared to SC or IC rats, potentially increasing local metabolic demands on microvasculature. Capillaries of EC rats were closer together than those of SC or IC rats and potentially filled a greater fraction of cortex with blood. The closer capillary spacing in young EC rats suggests compensatory angiogenesis in response to increased metabolic demand.

Hormone therapy is associated with smaller Achilles tendon diameter in active post-menopausal women.

The effects of hormonal status and activity levels on Achilles tendon structure were examined in asymptomatic post-menopausal women. It was hypothesized that women using hormone replacement therapy (HRT) would have better tendon structure than those not using HRT and that active women would have poorer tendon structure than inactive women. Eighty-five women including 53 active women (regular golf players) and 32 controls (healthy but inactive women) recorded their HRT and menopausal history and underwent basic anthropometric measurements. Women were divided into two groups based on their hormonal status: those currently using HRT; and those who had never used HRT or ceased using HRT at least 12 months prior to the study. Achilles tendons were examined with ultrasound and categorized as normal or abnormal, and the diameter of each tendon (mm) was recorded. Active women had a greater prevalence of tendon abnormality (P=0.10) and thicker Achilles tendons than inactive women (P<0.05). Active women on HRT had less tendon abnormality (P=0.056) than active women not on HRT and significantly less tendon thickness (P<0.05). This study indicates that Achilles tendon diameter is greater in active post-menopausal women. Hormone replacement therapy appeared to ameliorate this effect in active women. A similar effect from HRT on the Achilles tendons of inactive women was not apparent.

How a child builds its brain: some lessons from animal studies of neural plasticity.

Although the potential vulnerability of children's brain development is generally recognized, relatively little is known about the timing, resiliency, or mechanisms involved. While animal research should be applied only cautiously to human policy, some findings do have important clinical implications. This paper briefly reviews animal studies demonstrating the effects of experience on brain structure. Contemporary theories emphasize the self-organizing potential of brain structure, particularly regions that seem to have evolved for the purpose of storing information. We emphasize three major findings: (1) many regions of the brain are responsive to experience, but they differ in the types of information stored and in their developmental timing. (2) One type of plasticity is typically embedded in a developmental program, and it requires appropriate timing and quality of the information stored for the animal's development to be normal. (3) Another category of plasticity stores information that is idiosyncratic and unpredictable, but is often useful for species such as humans that learn throughout their life span. We therefore expect that some aspects of human brain development use the first type of plasticity and that abnormal experience or deprivation may cause lasting harm to brain and behavior. However, because the other type of plasticity lasts a lifetime, efforts such as psychotherapy or social interventions may help heal a wounded brain.

Lingual ectopia of the thyroid gland and autotransplantation.

A case of lingual ectopia of the thyroid gland in an adult patient is presented. The management by total excision and autotransplantation of the thyroid is described with a brief review of literature.

Experience and brain development.

This article considers how experience can influence the developing and mature brain and proposes a new categorization scheme based upon the type of information stored and the brain mechanisms that appear to be involved in storing it. In this scheme, experience-expectant information storage refers to incorporation of environmental information that is ubiquitous in the environment and common to all species members, such as the basic elements of pattern perception. Experience-expectant processes appear to have evolved as a neural preparation for incorporating specific information: in many sensory systems, synaptic connections between nerve cells are overproduced, and a subsequent selection process occurs in which aspects of sensory experience determine the pattern of connections that remains. Experience-dependent information storage refers to incorporation of environmental information that is idiosyncratic, or unique to the individual, such as learning about one's specific physical environment or vocabulary. The neural basis of experience-dependent processes appears to involve active formation of new synaptic connections in response to the events providing the information to be stored. Although these processes probably do not occur entirely independently of one another in development, the categories offer a new view more in accord with neural mechanisms than were terms like "critical" or "sensitive period."

Astrocyte hypertrophy in the dentate gyrus of young male rats reflects variation of individual stress rather than group environmental complexity manipulations.

Glial hypertrophy is associated with synaptogenesis in visual cortex and with stress-induced damage in the hippocampus. This study examined astrocytes in the dentate gyrus of male weanling rats exposed to complex or standard laboratory environments. No group differences in astrocytic surface density were observed, as expected in this brain region where group differences in synaptogenesis in male rats are reportedly minimal. Similarly, no group differences in adrenal weight were observed. Across all treatment groups, however, a significant positive correlation (r = 0.57) between adrenal weight and surface density of astrocytic processes was found. Considerable variation in responses of individual rats to their environments occurs in both the complex and the laboratory cage environments, and animals responding poorly may have had heavier adrenals and greater astrocyte reactivity in the dentate gyrus. Thus astrocyte hypertrophy in the dentate gyrus reflects the stress history of the individual rat and not any differential effects of rearing in a complex or a laboratory cage environment.