Closed-loop cervical epidural stimulation partially restores ipsilesional diaphragm EMG after acute C2 hemisection.

Cervical spinal cord injury creates lasting respiratory deficits which can require mechanical ventilation long-term. We have shown that closed-loop epidural stimulation (CL-ES) elicits respiratory plasticity in the form of increased phrenic network excitability (Malone et. al., E Neuro, Vol 9, 0426-21.2021, 2022); however, the ability of this treatment to create functional benefits for breathing function per se after injury has not been demonstrated. Here, we demonstrate in C2 hemisected anesthetized rats, a 20-minute bout of CL-ES administered at current amplitudes below the motor threshold restores paralyzed hemidiaphragm activity in-phase with breathing while potentiating contralesional activity. While this acute bout of stimulation did not elicit the increased network excitability seen in our chronic model, a subset of stimulated animals continued spontaneous ipsilesional diaphragm activity for several seconds after stopping stimulation. These results support the use of CL-ES as a therapeutic to rescue breathing after high cervical spinal cord injury, with the potential to lead to lasting recovery and device independence.

Complex migration history is revealed by genetic diversity of tomato samples collected in Italy during the eighteenth and nineteenth centuries.

Native to South America, the tomato is now grown almost worldwide. During its domestication and improvement, important selection signatures were fixed in certain agronomic and adaption traits. Such traits include fruit morphology, which became a major target for selection over the centuries. However, little is known about precisely when some mutations arose and how they spread through the germplasm. For instance, elongated fruit variants, originating both via mutations in SUN and OVATE genes, may have arisen prior to domestication or during tomato cultivation in Europe. To gain insights into the tomato admixture and selection pattern, the genome of two tomato herbarium specimens conserved in the Herbarium Porticense (PORUN) was sequenced. Comparison of the DNA of herbarium samples collected in Italy between 1750 and 1890 with that of living tomato accessions yielded insights into the history of tomato loci selection. Interestingly, the genotype of the more recent sample (LEO90), classified in 1890 as the oblungum variety, shows several private variants in loci implicated in fruit shape determination, also present also in wild tomato samples. In addition, LEO90, sampled in the nineteenth century, is genetically more distant from cultivated varieties than the SET17 genotype, collected in the eighteenth century, suggesting that elongated tomato varieties may originate from a cross between a landrace and a wild ancestor. Findings from our study have major implications for the understanding of tomato migration patterns and for the conservation of allelic diversity and loci recovery.

Individual- and community-level risk factors for ESBL Enterobacteriaceae colonization identified by universal admission screening in London.

OBJECTIVES: We evaluated risk factors for gastrointestinal carriage of Enterobacteriaceae which produce extended-spectrum ß-lactamases (ESBL-E), including individual-level variables such as antibiotic use and foreign travel, and community-level variables such as housing and deprivation. METHODS: In an observational study in 2015, all patients admitted to a London hospital group were approached to be screened for ESBL-E carriage using rectal swabs for 4 months. Patients completed a risk factor questionnaire. Those with a residential postcode in the local catchment area were linked to a database containing community-level risk factor data. Risk factors for ESBL-E carriage were determined by binary logistic regression. RESULTS: Of 4006 patients, 360 (9.0%) carried ESBL-E. Escherichia coli was the most common organism (77.8%), and CTX-M-type ESBLs were the most common genes (57.9% CTX-M-15 and 20.7% CTX-M-9). In multivariable analysis, risk factors for phenotypic ESBL-E among the 1633 patients with a residential postcode within the local catchment area were: travel to Asia (OR 4.4, CI 2.5-7.6) or Africa (OR 2.4, CI 1.2-4.8) in the 12 months prior to admission, two or more courses of antibiotics in the 6 months prior to admission (OR 2.0, CI 1.3-3.0), and residence in a district with a higher-than-average prevalence of overcrowded households (OR 1.5, CI 1.05-2.2). . CONCLUSIONS: Both individual and community variables were associated with ESBL-E carriage at hospital admission. The novel observation that household overcrowding is associated with ESBL-E carriage requires confirmation, but raises the possibility that targeted interventions in the community could help prevent transmission of antibiotic-resistant Gram-negative bacteria.

Identification of a zoonotic genotype 3 hepatitis E subtype in wildlife in north-eastern Italy.

Hepatitis E virus (HEV) is an emerging zoonosis caused by a positive RNA single stranded virus of the Hepeviridae family. In developed countries, pigs and wild boars are the main reservoir for zoonotic genotypes 3 and 4. In spring 2017, for the first time HEV was detected in wild boars captured in the Regional Park of the Euganean Hills, in north-eastern Italy. Phylogenetic analysis of two complete viral genomes and seven partial ORF1 and ORF2 sequences of HEV viruses, selected from twelve positive animals, showed that the viruses grouped together within genotype 3 but clustered separately from previously identified subtypes, thus suggesting the identification of a novel genotype 3 subtype. The phylogenetic analysis of nine partial ORF2 sequences showed the closest similarity with wild boar/human viruses identified in central-northern Italy in 2012. The circulation of HEVs in this area, characterized by a vast man-made environment, an overpopulation of wild boars and >150 swine farms, should be considered in a public health perspective. Further investigations at the wild/domestic species and human interface are therefore necessary to gain a deeper understanding of HEV dynamics.

Impact of sexual maturity on the welfare of immunocastrated v. entire heavy female pigs.

During oestrus, fattening female pigs are more prone to lameness, fractures and wounds due to mounting and agonistic behaviours of penmates. This study assessed the effect of sexual maturity on the behaviour and welfare of heavy female pigs slaughtered at 36 weeks of age (180±10 kg) for dry-cured ham production. An immunocastrated control group was used for comparison. In all, 56 15-week-old female pigs, individually identifiable by back tattoos were equally distributed among four pens. All animals from two pens were subject to a three-dose immunocastration schedule at 16, 20 and 32 weeks of age. Skin lesions and behaviours were assessed at 18, 23, 28, 33 and 36 weeks of age. A blood sample was collected at 20, 24, 28 and 32 weeks of age for assessing health/stress parameters and GnRH antibodies. At slaughter, ovaries were weighed, measured and histologically examined; stomachs, carcasses and lungs were scored for lesions and a further blood sample was taken. Immunocastrated pigs did not significantly differ from controls in growth rate, feed efficiency and slaughter performances (lung score, gastric score, backfat thickness). However, they showed a lower frequency of aggressive interactions at 33 and 36 weeks, lower front lesions at 28 weeks, but higher at 30 weeks; a lower haptoglobin level at 28 weeks, a lower level of cortisol and back lesions at slaughter (36 weeks). These findings suggest a low, yet not negligible, impact of sexual maturity on the welfare of heavy female pigs.

Secondary solid cancer following hematopoietic cell transplantation in patients with thalassemia major.

Hematopoietic cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers (SSCs). The aim of this retrospective study was to compare the incidence of SSC in a monocentric cohort of thalassemia major (TM) patients (n=122) who received HCT versus an hematopoietic cell donor monocentric cohort (n=122) and versus a large multicenter cohort of age- and sex-matched TM patients (n=244) who received conventional therapy. With a median follow-up of 24 years, 8 transplanted patients were diagnosed with SSC at a median of 18 years after HCT and at a median age of 33 years. Three patients died of cancer progression and 5 are living after a follow-up ranging from 10 months to 16 years after SSC diagnosis. The 30-year cumulative incidence of developing SSC was 13.24%. The occurrence of solid cancers in the hematopoietic cell donor cohort was limited to only one case for a significantly lower cumulative incidence (3.23%, P=0.02) and to 3 cases in the cohort of nontransplant patients for a significantly lower cumulative incidence (1.32%, P=0.005). This study shows that the magnitude of increased risk of SST is fourfold to sixfold for patients treated with HCT as compared with hematopoietic cell donors and nontransplant patients.

Hepatitis E virus infection in North Italy: high seroprevalence in swine herds and increased risk for swine workers.

We determined the hepatitis E virus (HEV) seroprevalence and detection rate in commercial swine herds in Italy's utmost pig-rich area, and assessed HEV seropositivity risk in humans as a function of occupational exposure to pigs, diet, foreign travel, medical history and hunting activities. During 2011-2014, 2700 sera from 300 swine herds were tested for anti-HEV IgG. HEV RNA was searched in 959 faecal pools from HEV-seropositive herds and in liver/bile/muscle samples from 179 pigs from HEV-positive herds. A cohort study of HEV seropositivity in swine workers (n = 149) was also performed using two comparison groups of people unexposed to swine: omnivores (n = 121) and vegetarians/vegans (n = 115). Herd-level seroprevalence was 75·6% and was highest in farrow-to-feeder herds (81·6%). Twenty-six out of 105 (24·8%) herds had HEV-positive faecal samples (25 HEV-3, one HEV-4). Only one bile sample tested positive. HEV seropositivity was 12·3% in swine workers, 0·9% in omnivores and 3·0% in vegetarians/vegans. Factors significantly associated with HEV seropositivity were occupational exposure to pigs, travel to Africa and increased swine workers' age. We concluded that HEV is widespread in Italian swine herds and HEV-4 circulation is alarming given its pathogenicity, with those occupationally exposed to pigs being at increased risk of HEV seropositivity.

Spatial Alignment and Response Hand in Geometric and Motion Illusions.

Perception of visual illusions is susceptible to manipulation of their spatial properties. Further, illusions can sometimes affect visually guided actions, especially the movement planning phase. Remarkably, visual properties of objects related to actions, such as affordances, can prime more accurate perceptual judgements. In spite of the amount of knowledge available on affordances and on the influence of illusions on actions (or lack of thereof), virtually nothing is known about the reverse: the influence of action-related parameters on the perception of visual illusions. Here, we tested a hypothesis that the response mode (that can be linked to action-relevant features) can affect perception of the Poggendorff (geometric) and of the Vanishing Point (motion) illusion. We explored the role of hand dominance (right dominant versus left non-dominant hand) and its interaction with stimulus spatial alignment (i.e., congruency between visual stimulus and the hand used for responses). Seventeen right-handed participants performed our tasks with their right and left hands, and the stimuli were presented in regular and mirror-reversed views. It turned out that the regular version of the Poggendorff display generates a stronger illusion compared to the mirror version, and that participants are less accurate and show more variability when they use their left hand in responding to the Vanishing Point. In summary, our results show that there is a marginal effect of hand precision in motion related illusions, which is absent for geometrical illusions. In the latter, attentional anisometry seems to play a greater role in generating the illusory effect. Taken together, our findings suggest that changes in the response mode (here: manual action-related parameters) do not necessarily affect illusion perception. Therefore, although intuitively speaking there should be at least unidirectional effects of perception on action, and possible interactions between the two systems, this simple study still suggests their relative independence, except for the case when the less skilled (non-dominant) hand and arguably more deliberate responses are used.

Pregnancy outcome following hematopoietic cell transplantation for thalassemia major.

The aim of this study was to investigate the methods of conception and delivery, as well as the course and outcome of 42 pregnancies occurring in 15 female patients (27 pregnancies) and partners of 8 male patients (15 pregnancies) with ß-thalassemia major who were successfully treated with allogeneic hematopoietic cell transplantation (HCT). Most pregnancies (n=21) were achieved with spontaneous conception in female patients. There were two miscarriages. Five pregnancies were late preterm. Delivery was vaginal in 4 cases and by caesarean section in 18. Overall, 22 term pregnancies resulted in successful deliveries of 23 neonates. Two of 23 neonates were symmetrical small for gestational age / intrauterine growth restriction. All 15 pregnancies that occurred in partners of men who received an allogeneic HCT were achieved with spontaneous conception. No miscarriage was observed. Overall, 14 term pregnancies resulted in successful deliveries of 14 live-born singletons. Delivery was vaginal in nine cases and by caesarean section in five. All infants were full-term. Many patients with ß-thalassemia major who received an allogeneic HCT retained or recovered their fertility after transplant. In these patients, pregnancy has been a practical and safe possibility and usually had a favorable outcome as in the normal population.

Embracing 21st Century Information Sharing: Defining a New Paradigm for the Food and Drug Administration's Regulation of Biopharmaceutical Company Communications with Healthcare Professionals.

The Food and Drug Administration (FDA) plays a unique role in protecting the public health and minimizing the risk of the distribution of unsafe or ineffective medicines in the United States. Perhaps equally as important for public health, however, is the need for healthcare professionals to be well informed about the benefits and risks of the medicines they prescribe. In this way, information sharing is critical to healthcare delivery. FDA's current interpretation of laws and regulations governing healthcare communications prohibits biopharmaceutical companies from sharing certain accurate, data-driven information about FDA-approved uses and medically accepted alternative uses of FDA-approved drugs with healthcare professionals. Often, these uses are the standard of care for good medical practice and are, accordingly, reimbursed under the federal healthcare programs. FDA has failed to describe adequately how manufacturers can share truthful and non-misleading information about such uses with healthcare professionals and formulary decision makers. This failure could impede medical innovation, negatively impact patient care, and increase healthcare costs. To improve public health, FDA should reform its current approach and provide manufacturers with a clear safe harbor on how to share data and information on both approved uses and medically accepted alternative uses of FDA-approved drugs with healthcare professionals. This Article describes key principles for a new regulatory paradigm.

Hepatitis E virus genotype 4 in a pig farm, Italy, 2013.

Zoonotic strains of hepatitis E virus (HEV) in Europe have been reported to belong to genotypes 3 and 4. In 2012 and 2013, 57 pig farms in Northern Italy that had previously resulted seropositive for HEV were surveyed for the presence of the virus, with positive samples subsequently genotyped. Hepatitis E RNA was identified in 17/57 (29·8%) seropositive farms. Phylogenetic analysis demonstrated that distinct subtypes of genotype 3 were circulating in the north-east of Italy; as well, for the first time in the Italian swine population, genotype 4 was identified and attributed to subtype d.

Implantable cardioverter defibrillator in sport participation.

Although athletic participation lowers cardiovascular risk and improves quality of life, it may represent a hazard in high-risk group athletes such as those with cardiac abnormalities receiving an implantable cardioverter defibrillator (ICD). ICD sports participants are exposed to the potential risk of inappropriate shocks due to sinus tachycardia and other supraventricular arrhythmias during exertion as well as device injury. The safety of athletic participation of ICD-patients is not completely defined and ICD efficacy in interrupting malignant arrhythmias during intense exercise is partly unknown. This explains difficulties in current recommendations made by physicians, given the associated potentially ischemic, autonomic and metabolic conditions. The scope of this review is to underline specific considerations including potential risks and recommendations for athletic participation in this patient-group.

Application of an integrated outbreak management plan for the control of leptospirosis in dairy cattle herds.

SUMMARY: Two outbreaks of Leptospira borgpetersenii serovar Hardjo infection in dairy cattle herds were managed through the application of enhanced biosecurity measures, whole-herd antibiotic treatment and vaccination. Micro-agglutination test antibody titres were determined in paired serum samples at 3 weeks (T1: n = 125, 97% seropositivity, median 800, range 100-12 800) and 24 weeks (T2: n = 110, 88% seropositivity, median 200, range 100-6400) after vaccination and studied in relation to cows' age, herd of origin and sampling time. From T1 to T2, vaccine-elicited antibody titres decreased by 84·7% (95% CI 76·2-90·1). Consistent with increasing immunocompetence in calves (aged <12 months) and immunosenescence in adult cows (aged >36 months) associated with ageing, antibody titres correlated positively with calves' age and negatively with adult cows' age. No cow had cultivable, (histo)pathologically detectable and/or PCR-detectable leptospires in urine or kidney samples after treatment and vaccination. Vaccination together with proper biosecurity measures and chemoprophylaxis are an affordable insurance to control bovine leptospirosis.

How To Achieve Durable Pulmonary Vein Antral Isolation?

The inability to achieve durable pulmonary vein isolation(PVI) remains a major limitation to a catheter ablation for thew treatment of atrial fibrillation(AF), potentially resulting in AF recurrence.In this review,we discuss the research performed investigating methods to improve lesion permanence for the goal of durable PVI.Investigations evaluted procedural techniques,various catheres utilized, adjunctive pharamacologic therapy and novel energy sources designed to improve ablation lesion permanence are discussed.

Enantiomeric separation of amlodipine and its two chiral impurities by nano-liquid chromatography and capillary electrochromatography using a chiral stationary phase based on cellulose tris(4-chloro-3-methylphenylcarbamate).

In this work, a novel polysaccharide-based chiral stationary phase, cellulose tris(4-chloro-3-methylphenylcarbamate), also called Sepapak 4 has been evaluated for the chiral separation of amlodipine (AML) and its two impurities. AML is a powerful vasodilatator drug used for the treatment of hypertension. Capillary columns of 100 µm id packed with the chiral stationary phase were used for both nano-LC and CEC experiments. The optimization of the mobile phase composed of ACN/water, (90:10, v/v) containing 15 mM ammonium borate pH 10.0 in nano-LC allowed the chiral separation of AML and the two impurities, but not in a single run. With the purpose to obtain the separation of the three pairs of enantiomers simultaneously, CEC analyses were performed in the same conditions achieving better enantioresolution and higher separation efficiencies for each compound. To fully resolve the mixture of six enantiomers, parameters such as buffer pH and concentration sample injection have been then investigated. A mixture of ACN/water (90:10, v/v) containing 5 mM ammonium borate buffer pH 9.0 enabled the complete separation of the three couples of enantiomers in less than 30 min. The optimized CEC method was therefore validated and applied to the analysis of pharmaceutical formulation declared to contain only AML racemate.

Which are the most reliable predictors of recurrence of atrial fibrillation after transcatheter ablation?: a meta-analysis.

CONTEXT: Transcatheter ablation of atrial fibrillation (AF) has undergone important development, with acceptable midterm results in terms of the safety and recurrence. A meta-analysis was performed to identify the periprocedural complications, midterm success rates and predictors of recurrence after AF ablation. METHODS AND RESULTS: 4357 patients with paroxysmal AF, 1083 with persistent AF and 1777 with long standing AF were included. The pooled analysis showed that there was an in-hospital complication rate of tamponade requiring drainage of 0.99% (0.44-1.54; CI 99%), stroke with neurological persistent impairment of 0.22% (0.04-0.47; CI 99%), and stroke without of 0.36% (0.03-0.70; CI 99%) After a follow up of 22 (13-28) months and 1.23 (1.19-1.5; CI 99%) procedures per patient, the AF recurrence rate was 31.20% (24.87-34.81; CI 99%). The persistent AF patients exhibited a greater risk of recurrence after the first ablation (OR 1.78 [1.14, 2.77] CI 99%), but a trend towards non significance was present in the patients with more than one procedure (OR 1.69 [0.95, 3.00] CI 99%). The most powerful predictors of an AF ablation failure in the overall population were a recurrence within 30-days (OR 4.30; 2.00-10.80), valvular AF (OR 5.20; 2.22-9.50) and a left atrium diameter of more than 50mm (OR 5.10 2.00-12.90; all CI 95%). CONCLUSIONS: Persistent AF remains burdened from higher recurrence rates, however not so following redo-procedures. Three predictors, valvular AF, a left atrium diameter longer than 50mm and recurrence within 30 days, could be appraised to drive selection of patients and therapeutic strategy.

Old and new diagnostic approaches for Q fever diagnosis: correlation among serological (CFT, ELISA) and molecular analyses.

The objective of this study was to evaluate the performance of the complement fixation test (CFT) with respect to ELISA for the serological diagnosis of Q fever and to assess the role of serology as a tool for the identification of the shedder status. During 2009-2010, sera from 9635 bovines and 3872 small ruminants (3057 goats and 815 sheep) were collected and analyzed with CFT and ELISA. In addition, 2256 bovine, 139 caprine and 72 ovine samples (individual and bulk tank milk samples, fetuses, vaginal swabs and placentae) were analyzed with a real-time PCR kit. The relative sensitivity (Se) and specificity (Sp) of CFT with respect to ELISA were Se 26.56% and Sp 99.71% for cattle and Se 9.96% and Sp 99.94% for small ruminants. To evaluate the correlation between serum-positive status and shedder status, the ELISA, CFT and real-time PCR results were compared. Due to the sampling method and the data storage system, the analysis of individual associations between the serological and molecular tests was possible only for some of the bovine samples. From a statistical point of view, no agreement was observed between the serological and molecular results obtained for fetus and vaginal swab samples. Slightly better agreement was observed between the serological and molecular results obtained for the individual milk samples and between the serological (at least one positive in the examined group) and molecular results for the bulk tank milk (BTM) samples. The CFT results exhibited a better correlation with the shedder status than did the ELISA results.

Left ventricular ejection fraction for the risk stratification of sudden cardiac death: friend or foe?

More than 450000 Americans die suddenly each year from sustained ventricular tachycardia or fibrillation. A correct identification of these patients is crucial for a rational clinical management, because the demonstrated effectiveness of implantable cardioverter-defibrillators (ICD) on the reduction of sudden cardiac death. Basing on the results of multiple clinical trials, left ventricular systolic function, measured as ejection fraction, is currently the only recommended tool to identify patients at higher risk of sudden death that would benefit from a prophylactic ICD. However, the systematic implementation of prophylactic ICD recommendations results in a substantial number of inappropriate ICD implantations, while failing to prevent the majority of sudden deaths occurring in the general population. That has been the case implementing arrhythmic risk stratification with a rough arrhythmic risk marker, such as ejection fraction, that lacks sensitivity and specificity in the prediction of sudden cardiac death. The aim of this viewpoint is to critically revise the value of ejection fraction in the identification of patients at risk of sudden cardiac death.