COVID-19 vaccination and drug users: Past, present, and future.

Vaccination against COVID-19 is crucial in the attempt of containing the virus' spread, but facing a viral pathogen with such a high prevalence means that vaccination strategies are facing an unprecedented situation. People that use illicit drugs may have elevated risk of adverse outcomes from COVID-19 given their high prevalence of underlying medical conditions, including respiratory and pulmonary disease, chronic liver disease, cardiovascular and cerebrovascular conditions, diabetes, and compromised immune systems. Despite a widespread distribution on the Italian territory, a large presence of health personnel and a long-standing experience in vaccinations, addiction clinics have yet to be involved in the vaccination campaign against COVID-19. The aim of this study was to investigate the beliefs of drug users attending some Italian addiction clinics, in order to envisage any vaccine administration strategies involving the services themselves. A questionnaire used for the Italian general population to investigate the relative importance of some factors in influencing the propensity to vaccinate against COVID-19, was administrated to drug users in a multicenter survey. The majority of respondents expressed general confidence in vaccines and a good willingness to undergo vaccination. Given strong peer networks, high coverage of treatment and harm reduction interventions, Italian public addiction clinics could play a strategic role in administering the vaccine in this hard-to-reach population, usefully aiding the global campaign against the virus.

Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury.

Neurological dysfunctions are the most impactful and persistent consequences of traumatic brain injury (TBI). Indeed, previous reports suggest that an association between TBI and chronic pain syndromes, as well anxio-depressive behaviors, tends to be more common in patients with mild forms of TBI. At present, no effective treatment options are available for these symptoms. In the present study, we used a weight drop mild TBI mouse model to investigate the effect of a commercially available 10% Cannabidiol (CBD) oil on both the sensorial and neuropsychiatric dysfunctions associated with mild TBI through behavioral and biomolecular approaches. TBI mice developed chronic pain associated with anxious and aggressive behavior, followed by a late depressive-like behavior and impaired social interaction. Such behaviors were related with specific changes in neurotransmitters release at cortical levels. CBD oral treatment restored the behavioral alterations and partially normalized the cortical biochemical changes. In conclusion, our data show some of the brain modifications probably responsible for the behavioral phenotype associated with TBI and suggest the CBD as a pharmacological tool to improve neurological dysfunctions caused by the trauma.

An accreting pulsar with extreme properties drives an ultraluminous x-ray source in NGC 5907.

Ultraluminous x-ray sources (ULXs) in nearby galaxies shine brighter than any x-ray source in our Galaxy. ULXs are usually modeled as stellar-mass black holes (BHs) accreting at very high rates or intermediate-mass BHs. We present observations showing that NGC 5907 ULX is instead an x-ray accreting neutron star (NS) with a spin period evolving from 1.43 seconds in 2003 to 1.13 seconds in 2014. It has an isotropic peak luminosity of [Formula: see text]1000 times the Eddington limit for a NS at 17.1 megaparsec. Standard accretion models fail to explain its luminosity, even assuming beamed emission, but a strong multipolar magnetic field can describe its properties. These findings suggest that other extreme ULXs (x-ray luminosity [Formula: see text] 1041 erg second[Formula: see text]) might harbor NSs.

D-Aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice.

D-Aspartate (D-Asp) is a free D-amino acid detected in multiple brain regions and putative precursor of endogenous N-methyl-D-aspartate (NMDA) acting as agonist at NMDA receptors. In this study, we investigated whether D-Asp (20 mM) in drinking solution for 1 month affects pain responses and pain-related emotional, and cognitive behaviour in a model of neuropathic pain induced by the spared nerve injury (SNI) of the sciatic nerve in mice. SNI mice developed mechanical allodynia and motor coordination impairment 30 days after SNI surgery. SNI mice showed cognitive impairment, anxiety and depression-like behaviour, reduced sociability in the three chamber sociability paradigm, increased expression of NR2B subunit of NMDA receptor and Homer 1a in the medial prefrontal cortex (mPFC). The expression of (post synaptic density) PSD-95 and Shank 1was instead unaffected in the mPFC of the SNI mice. Treatment with D-Asp drinking solution, started right after the SNI (day 0), alleviated mechanical allodynia, improved cognition and motor coordination and increased social interaction. D-Asp also restored the levels of extracellular D-Asp, Homer 1a and NR2B subunit of the NMDA receptor to physiological levels and reduced Shank1 and PSD-95 protein levels in the mPFC. Amitriptyline, a tricyclic antidepressant used also to alleviate neuropathic pain in humans, reverted mechanical allodynia and cognitive impairment, and unlike D-Asp, was effective in reducing depression and anxiety-like behaviour in the SNI mice and increased PSD protein level. Altogether these findings demonstrate that D-Asp improves sensorial, motor and cognitive-like symptoms related to chronic pain possibly through glutamate neurotransmission normalization in neuropathic mice.

A variable absorption feature in the X-ray spectrum of a magnetar.

Soft-γ-ray repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are slowly rotating, isolated neutron stars that sporadically undergo episodes of long-term flux enhancement (outbursts) generally accompanied by the emission of short bursts of hard X-rays. This behaviour can be understood in the magnetar model, according to which these sources are mainly powered by their own magnetic energy. This is supported by the fact that the magnetic fields inferred from several observed properties of SGRs and AXPs are greater than-or at the high end of the range of-those of radio pulsars. In the peculiar case of SGR 0418+5729, a weak dipole magnetic moment is derived from its timing parameters, whereas a strong field has been proposed to reside in the stellar interior and in multipole components on the surface. Here we show that the X-ray spectrum of SGR 0418+5729 has an absorption line, the properties of which depend strongly on the star's rotational phase. This line is interpreted as a proton cyclotron feature and its energy implies a magnetic field ranging from 2 × 10(14) gauss to more than 10(15) gauss.

Datura stramonium intake: a report on three cases.

This article describes three cases of Datura stramonium intake on two nonconsecutive days. In the first case, the patient took a small amount of D. stramonium seeds without showing any symptoms of intoxication. The other two patients had taken a considerable amount of seeds and reported a sudden surge in strength and energy, with some aggressive compulsion towards their peers. They showed delirium as well as confusion and disorientation. The absence of any specific legislation makes D. stramonium a tempting alternative to other psychoactive substances. Thus, it is extremely important to be able to recognize its symptoms so as to be able to diagnose any signs of intoxication properly.

Treatment of pilonidal sinus with primary closure. A twenty-year experience.

From 1985 to 2004, 229 patients (171 M, 58 F) aged from 16 to 35 years, affected by pilonidal sinus were treated by complete excision of the sinus and primary closure. Primary healing was achieved in 208 patients (91%) in an average time of 11.9 days. Secondary healing was achieved in 21 patients (9%) in 16-19 days. The mean postoperative hospital stay was 1.9 days and the average time off work 16 days. Recurrent pilonidal sinus was observed in 10 patients with a mean follow-up of 18 months (range: 12-24). On the basis of their experience, the authors conclude that complete excision of the pilonidal sinus with primary closure yields good results in terms of healing, morbidity, early return to work and recurrence rate and can be considered the treatment of choice for pilonidal sinus.

An open randomized study of the treatment of escitalopram alone and combined with gamma-hydroxybutyric acid and naltrexone in alcoholic patients.

gamma-hydroxybutyric acid (GHB) and the selective serotonin reuptake inhibitor escitalopram are effective in inducing and maintaining abstinence in alcohol. Naltrexone (NTX), an opioid antagonist, may be effective in preventing relapse in alcohol-dependent subjects. To evaluate whether each drug and its combination help to maintain alcohol abstinence, we determined the relapse rate over 6 months in 3 groups of patients. Group 1 (11 patients) received escitalopram (20 mg/day) orally administered; group 2 (12 patients) received NTX (50 mg/day) and escitalopram (20 mg/day); group 3 (12 patients) received GHB (75 mg/kg body weight) and escitalopram (20 mg/day); and group 4 (12 patients) received NTX (50mg/day) plus GHB (75 mg/kg) and escitalopram (20 mg/day). All groups received psychological support and underwent urine tests for alcohol metabolites twice a week. In group 1 (escitalopram only), 6 patients relapsed within 3 months and 3 after 6 months; whereas 2 patients remained abstinent. In group 2 (SSRI+NTX), 5 patients relapsed after 3 months and 3 after 6 months; whereas 4 patients remained abstinent. In group 3 (GHB+SSRI), 3 patients relapsed after 3 months and 3 after 6 months; whereas 6 patients remained abstinent. Finally, in group 4 (NTX+GHB+SSRI), 1 patient relapsed after 3 months and 1 after 6 months, whereas 10 patients remain abstinent. In conclusion, the combination of NTX+GHB+SSRI was the most effective in preventing relapses.

[Fecal incontinence: role of anal sphincter rehabilitation]. / Incontinenza fecale: ruolo della riabilitazione.

Fecal incontinence is a highly disabling symptom which causes the patient to gradually abandon all forms of social, family and working relationships. Rehabilitation was adopted initially in cases of surgical failure and considered as being only palliative. In our study we tested an original rehabilitation protocol for faecal incontinence which embraces 3 methods--physio-kinesitherapy, electrostimulation and biofeedback--in what we have called "anal sphincter functional rehabilitation". The study was conducted in 196 patients (61 M, 135 F) mean age 42.9 (range: 11-86), with faecal incontinence of varying aetiology. The 3 methods were carried out simultaneously in 3 one-hour sessions a week. The protocol envisaged 15 consecutive sessions at the end of which a first assessment was made of the results achieved. Therapeutic success was achieved in 93.4% of cases. The results obtained with our protocol do not differ from those reported by other Authors and we can therefore state that functional rehabilitation of the anal sphincter is to be viewed not merely as a valid alternative to surgery, but as the therapy of choice for fecal incontinence.

[Constipation. Proposal for a new classification and therapy]. / Outlet obstruction defecation. Proposta di un nuovo inquadramento e terapia.

The Authors propose a new classification for constipation according to which 84 patients were selected (63 females, 21 males) for a functional rehabilitation programme. Patients were subjected to a diagnostic protocol involving the performance of a number of instrumental tests. Degree and symptomatology of constipation were established by taking the clinical history of the patient. The rehabilitation protocol involved the simultaneous performance of physiokinesitherapy, electrostimulation and biofeedback of the pelvic floor. Patients underwent 3 weekly sessions, each lasting 60 minutes, over a series of 15 consecutive sessions, followed by a series of 6 consecutive sessions every three months. One-year results showed that 77 patients (92%) reported achieving regular intestinal activity with at least one evacuation a day and at intervals of no more than 3 days, and with a modification of faecal consistency and discontinuation of laxatives and/or cathartics. The other 7 patients (8%) continued using laxatives at a minimal dosage but had an improved evacuation rate and faecal consistency. The results show that many patients with constipations can undergo rehabilitation procedures with encouraging and remarkable therapeutic success.

[Pathophysiological and clinical trials of the abdominal compartment syndrome]. / Fisiopatologia e clinica della sindrome compartimentale addominale.

The abdominal compartment syndrome (ACS) is defined a situation of high degrade abdominal hypertension (IAH) with clinicals signs of multiorganic dysfunction. It's observed like in the intensive care, in particular surgycals and postraumatics, there is ever a bigger frequence of complications presented by criticals patients. The various trials remark a changeable incidence, but the common factor is characterized by a particular severity of scores. All the possibles mechanicals, haemorragicals, infiammatories, and postraumatics causes act, but don't enable the stability among abdominal content, abdominal compliance and parietal tension. The initial triad of effects is constitued by the elevation of diaphragm and the visceral and vascular compression; after this triad provoke a pathophysiologic system that, through various levels, bring to a respiratory, renal and cardiocirculatory dysfunction and to a parietal, hepatic and intestinal ischemia with consequent bacterical translation: sepsis and MOF. The Burch's classification (1996) report four levels of gravity by the slight (< 15 mmHg) to the heavyest (> 35 mmHg): the firsts two levels are of intensivistic competence and for the detention are used conservatives metodics and pharmacological approach; instead in the lasts two levels it's necessary to foresee a surgycal treatment of laparotomy, washing and drainage with following temporary paret's closure. The mortality is now very elevated (29-62%) especially when it's already established a multiorganical dysfunction; therefore it's necessary forward its appearance through the monitorization of abdominal pression (IAP) with the measurement of vescical pression in alls criticals patients at the aim to treat immediately the firsts signs of IAH.

Naltrexone plus benzodiazepine aids abstinence in opioid-dependent patients.

Naltrexone (NTX) is widely used to prevent relapse of opioid-dependent patients but its association with insomnia and "hyperexcitability" can result in treatment withdrawal. We evaluated whether NTX combined with the benzodiazepine prazepam was more effective than NTX in keeping patients opioid-free. We determined the relapse rate over 6 months in 56 opioid-dependent subjects, divided into 4 equal groups. All groups received psychological support and underwent urine tests for drug metabolites twice weekly. Group 1 did not receive pharmacological treatment (controls). Group 2 received NTX alone (one 50-mg tablet daily); group 3 received NTX (one 50-mg tablet daily) plus placebo (one tablet twice daily); and group 4 received NTX (one 50-mg tablet daily) plus prazepam (one 10-mg tablet twice daily). Ten patients of group 1 relapsed within 3 months, one after 6 months and three remained opioid-free. Six patients of group 2 relapsed within three months, two after 6 months, and six remained opioid-free. Seven patients of group 3 relapsed three months, one after 6 months and six patients remained opioid-free. In group 4, one patient relapsed within 3 months and one patient after 6 months; 12 patients of this group remained opioid-free. At urine tests, a significantly higher percent patients of group 4 remained free of Delta(9)-tetrahydrocannabinol versus patients of groups 2 and 3. In conclusion, many patients remained opioid-free on NTX alone or combined with prazepam, with a significant advantage for the NTX plus prazepam group.

[Emergency surgery for colorectal cancer: our experience]. / Le neoplasie del grosso intestino in urgenza: nostra esperienza.

Colorectal cancers have an extremely negative prognosis in the elderly, with a high percentage of clinical presentations requiring emergency surgery and high perioperative mortality rates. The clinical manifestations of this type of cancer set in a cutely in 20% of cases due to the sudden onset of one of the basic complications. The authors report on their experience with 79 patients undergoing emergency surgery for colorectal cancer. The choice of operation was made on the basis of the patient's general condition, as estimated by his or her ASA score, and the presence of associated diseases.

Interactive role of adenosine and dopamine in the opiate withdrawal syndrome.

Adenosine reduces opioid withdrawal symptoms by activating A(1) adenosine receptors, probably by inhibiting excitatory amino acid release. Since blockade of A(2A) adenosine receptors seems to enhance dopaminergic striatopallidal transmission, we evaluated the role of the purinergic system in the opiate withdrawal syndrome by using two A(1) receptor agonists [ N(6)-cyclohexyladenosine, CHA and 2-chloro- N(6)-cyclopentyladenosine, CCPA], and two A(2A) receptor antagonists (SCH 58261 and 8-(3-chlorostyryl)caffeine, CSC). Male adult rats received increasing doses of morphine sulphate suspended in 5 ml/kg of a sustained release preparation (40-100 mg/kg s.c.) daily for 4 days and 20 h after the last administration, the withdrawal syndrome was evoked by naloxone (5 mg/kg i.p.). Animals were observed for 30 min for signs of opiate withdrawal. Other groups of rats were implanted with concentric probes for microdialysis and dopamine levels were measured in the nucleus accumbens. CHA and CCPA (0.05, 0.1 or 0.5 mg/kg i.p.) significantly reduced "wet-dog" shakes, diarrhoea, teeth chattering, jumping and writhing. SCH 58261 and CSC (0.1, 0.5 or 1 mg/kg i.p.), given 10 min before naloxone, also reduced signs of opiate withdrawal. CHA plus SCH 58261 and CCPA plus CSC greatly enhanced the reduction of withdrawal signs observed with CHA and CCPA or CSC and SCH 58261 alone. In vivo microdialysis showed that naloxone significantly decreased DA release; this effect was prevented by pretreatment with systemic SCH 58261 and CSC, but not with CHA and CCPA. Our results demonstrate that A(1) and A(2A) adenosine receptors mediate the effect induced by adenosine in opiate withdrawal syndrome and suggest that adenosine A(1) agonists and adenosine A(2A) antagonists may be beneficial in the treatment of this syndrome.