Effect of sensory stimulus on striatal dopamine release in humans and cats: a [(11)C]raclopride PET study

BACKGROUND: Sensory stimulation of the forelimb extremities constitutes a well-established experimental model that has consistently shown to activate dopamine (DA) neurotransmission in the mammals' forebrain. OBJECTIVES: To visualize in vivo this modification of striatal DA release in healthy human volunteers using Positron Emission Tomography (PET) and [(11)C]raclopride. Experiments in humans were paralleled by experiments in anesthetized cats. Changes in endogenous DA release were assessed through its competition with [(11)C]raclopride binding (BP(raclo)), a radioligand probing DA D2-receptors. RESULTS: In humans no significant difference of BP(raclo) in caudate (with sensory stimulation: 2.0 +/- 0.3 versus without sensory stimulation: 2.2 +/- 0.3; P = 0.3) or putamen (2.6 +/- 0.3 versus 2.6 +/- 0.2; P = 0.9) ipsilateral to the stimulus was disclosed as a result of sensory stimulation. Similarly, no change of BP(raclo) was observed contralaterally to the stimulation in the caudate nucleus (with sensory stimulation: 2.0 +/- 0.4 versus without sensory stimulation: 2.1 +/- 0.2; P = 0.5) and the putamen (2.5 +/- 0.4 versus 2.6 +/- 0.2; P = 0.4). In cats the same results were obtained in the ipsilateral to stimulation striatum (with sensory stimulation: 2.5 +/- 0.03 versus without sensory stimulation: 2.4 +/- 0.05; P = 0.7). No change was also observed contralaterally to the stimulation (2.4 +/- 0.04 versus 2.5 +/- 0.06; P = 0.6). The [(11)C]raclopride binding remained unchanged by sensory stimuli in both humans and cats. CONCLUSION: This suggests that the DA release induced by sensory stimulus is mostly extrasynaptic whereas the synaptic DA release is probably small, which fits well with the absence of [(11)C]raclopride displacement. The mechanism of this extrasynaptic DA release could be related to a local action of glutamate on dopaminergic terminals via a thalamo-cortico-striatal loop. Present results also underline homology between cat and human responses to sensory stimuli and validate the use of cat brain to find physiological concepts in humans.     

Structure and function of DNA binding proteins from revertants of adenovirus type 5 mutants with a temperature-sensitive DNA replication

H5ts107 and H5ts125 are two adenoviruses type 5 (Ad5) mutants with a temperature-sensitive DNA replication. Both mutants contain an altered gene encoding the DNA binding protein (DBP). We have established by nucleotide sequence analysis that both mutants carry exactly the same mutation in the DBP gene resulting in the substitution of a proline residue at position 413 in the wild-type DBP amino acid sequence (529 amino acid residues long) by a serine residue. Revertants of H5ts107 and H5ts125, which are temperature independent in plaque efficiency and growth in HeLa cells at 32 degrees and 39 degrees, were characterized by nucleotide sequence analysis of their DBP genes. Four types of revertants could be distinguished: revertants with the wild-type DBP amino acid sequence (type I) and, revertants carrying, in addition to the original H5ts107/H5ts125 mutation at position 413, intragenic second site mutations at position 508 histidine leads to tyrosine (type II), at position 352 glycine leads to aspartic acid (type III), and at position 347 alanine leads to proline (type IV), respectively. All intragenic second site mutations are located, together with the H5ts107/H5ts125 mutation, in the C-terminal 45-kD fragment of the adenovirus DBP molecule. This provides further evidence that this part of the DBP molecule plays an important role in viral DNA replication. Phenotypic characterization of the revertants (J.C. Nicolas, F. Suarez, A.J. Levine, and M. Girard (1981), Virology 108, 521-524; (J.C. Nicolas, D. Ingrand, P. Sarnow, and A.J. Levine (1982), Virology 122, 481-485) has shown that the second site mutations reveal additional functional domains in the DBP molecule.     

Interferon-γ is essential for the development of cerebral malaria

Infection with Plasmodium berghei ANKA (PbA) causes fatal cerebral malaria (CM). While a pathogenic role for tumor necrosis factor (TNF) has been established, we asked whether a disruption of interferon-γ (IFN-γ) signaling would modulate CM. We demonstrate here that IFN-γR-deficient mice are completely protected from CM. PbA-induced release of TNF and up-regulation of endothelial intercellular adhesion molecule (ICAM)-1 expression, recruitment of mononuclear cells, and cerebral microvascular damage with vascular leakage occur only in wild-type mice. Protected mice die at a later time of severe anemia and overwhelming parasitemia. Resistance to CM in IFN-γR-deficient mice is associated with reduced serum TNF levels, reduced interleukin-12 expression in the brain and increased T-helper 2 cytokines. In conclusion, IFN-γ is apparently required for PbA-induced endothelial ICAM-1 up-regulation and subsequent microvascular pathology, resulting in fatal CM. In the absence of IFN-γ signaling, ICAM-1 and TNF up-regulation is reduced; hence, PbA infection fails to cause fatal CM.     

Effects of training at simulated altitude on performance and muscle metabolic capacity in competitive road cyclists

Summary Differences between the effects of training at sea level and at simulated altitude on performance and muscle structural and biochemical properties were investigated in 8 competitive cyclists who trained for 3–4 weeks, 4–5 sessions/week, each session consisting of cycling for 60–90 min continuously and 45–60 min intermittently. Four subjects, the altitude group (AG), trained in a hypobaric chamber (574 torr=2300 m above sea level), and the other four at sea level (SLG). Before and after training work capacity was tested both at simulated altitude (574 torr) and at sea level, by an incremental cycle ergometer test until exhaustion. Work capacity was expressed as total amount of work performed. Venous blood samples were taken during the tests. Leg muscle biopsies were taken at rest before and after the training period. AG exhibited an increase of 33% in both sea level and altitude performance, while SLG increased 22% at sea level and 14% at altitude. Blood lactate concentration at a given submaximal load at altitude was significantly more reduced by training in AG than SLG. Muscle phosphofructokinase (PFK) activity decreased with training in AG but increased in SLG. All AG subjects showed increases in capillary density. In conclusion, work capacity at altitude was increased more by training at altitude than at sea level. Work capacity at sea level was at least as much improved by altitude as by sea level training. The improved work capacity by training at altitude was paralleled by decreased exercise blood lactate concentration, increased capillarization and decreased glycolytic capacity in leg muscle.     

Transition to virtual clinic: Experience in a multidisciplinary clinic for Down syndrome

The COVID‐19 pandemic necessitated a rapid transition from in‐person office visits to virtual visits in the Down syndrome specialty program at Massachusetts General Hospital (MGH DSP). We describe the clinic transition to virtual visits in April 2020 and reflect on our six‐month experience in virtual visits. Clinic metrics were tracked. Electronic survey responses were collected from caregivers attending virtual visits. Input from the MGH DSP team was collected. From April to September 2020, we maintained patient volume (45 visits per month) and overall satisfaction score (6.7 out of 7) following a sudden, unanticipated transition to virtual visits. Survey of 17 caregivers attending virtual visits found that most were equipped with technology, had access to a private location, and most were able to access visit without any limitations. Caregivers appreciated the convenience of virtual visits but sometimes missed the personal connection of an in‐person visit. Overall, though, virtual visits were frequently viewed as no different than office visits. Team members identified benefits and challenges of virtual visits, as well as lessons learned from this transition. We were able to maintain multidisciplinary, specialty care with optimal caregiver feedback and sustained number of patient visits.     

Restriction fragment pattern analysis of genomes from French isolates of suis herpes virus 1 (Aujeszky's disease virus)

Summary Purified DNA from 45 isolates of suis herpes virus 1 (SHV1) collected between 1980 and 1987 from clinical outbreaks of Aujeszky's disease on French farms was compared by restriction fragment pattern (RFP) analysis. The BamHI generated RFPs were found to be distinguishable, confirming RFP analysis as a potential epidemiological tool. The RFP could be assigned to two established major electrophoretic types and different subtypes. The RFP analysis indicated that the majority of outbreaks were caused by ADV with a central European genome type. The heterogeneity of RFPs among PRV isolates recovered from the central nervous system, lung, and foetus was not restricted specifically to one clinical entity. Variations in the virulence of the 45 isolates studied in mice, chicks, or piglets were unrelated to the RFP subtypes. One unusual RFP has been described for one strain of low virulence.     

Mg2+ Transporters in Digestive Cancers

Despite magnesium (Mg²⁺) representing the second most abundant cation in the cell, its role in cellular physiology and pathology is far from being elucidated. Mg²⁺ homeostasis is regulated by Mg²⁺ transporters including Mitochondrial RNA Splicing Protein 2 (MRS2), Transient Receptor Potential Cation Channel Subfamily M, Member 6/7 (TRPM6/7), Magnesium Transporter 1 (MAGT1), Solute Carrier Family 41 Member 1 (SCL41A1), and Cyclin and CBS Domain Divalent Metal Cation Transport Mediator (CNNM) proteins. Recent data show that Mg²⁺ transporters may regulate several cancer cell hallmarks. In this review, we describe the expression of Mg²⁺ transporters in digestive cancers, the most common and deadliest malignancies worldwide. Moreover, Mg²⁺ transporters’ expression, correlation and impact on patient overall and disease-free survival is analyzed using Genotype Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. Finally, we discuss the role of these Mg²⁺ transporters in the regulation of cancer cell fates and oncogenic signaling pathways.     

Altersspezifische Trends des risikoreichen Alkoholkonsums in Deutschland: Parallele oder unterschiedliche Verläufe?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Nach der Collectivity-of-Drinking-Cultures-Theorie von Skog finden Veränderungen des Alkoholkonsums in allen...     

Highly Pathogenic Avian Influenza A(H5N8) Virus Spread by Short- and Long-Range Transmission,France, 2016–17

We detected 3 genotypes of highly pathogenic avian influenza A(H5N8) virus in France during winter 2016–17. Genotype A viruses caused dramatic economic losses in the domestic duck farm industry in southwestern France. Our phylogenetic analysis suggests that genotype A viruses formed 5 distinct geographic clusters in southwestern France. In some clusters, local secondary transmission might have been started by a single introduction. The intensity of the viral spread seems to correspond to the density of duck holdings in each production area. To avoid the introduction of disease into an unaffected area, it is crucial that authorities limit the movements of potentially infected birds.     

Head-to-head comparison of prostatic urethral lift and water vapor thermal therapy for the treatment of symptomatic benign prostatic hyperplasia: a real-life study

Purpose

This study aimed at reporting a head-to-head comparison between water vapor thermal therapy using the Rezūm? system and prostatic urethral lift using the Urolift? system in men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH).

Patients and methods

From December 2017 to November 2019, consecutive patients who underwent Rezūm? and Urolift? procedures in two urology centers have been retrospectively considered. Only patients with a prostate size less than 80 mL were included. We used the PSM method to adjust baseline differences between both groups. The co-primary endpoint included the change in International Prostate Symptom Score (IPSS) and IPSS- quality of life (QoL) from baseline to 12 months.

Results

A total of 61 (52.1%) and 56 (47.9%) patients underwent Rezum? and Urolift? procedures, respectively. After PSM adjustment, 24 patients were included in both groups. No serious adverse events occurred (>?Clavien II) in both groups. At 12 months, higher IPSS improvement was observed in the Rezum? group (median:4 [IQR 3–5]) than in the Urolift? group (median:8 [IQR 7–12]), without statistical difference (p?=?0.08). The improvement in term of QoL at 12 m was similar (p?=?0.43). The retreatment rates were 25% (Urolift?) and 8.3% (Rezum?), p?=?0.24. Erection and ejaculatory function scores did not change significantly in either treatment group. Results in the full cohort showed that Rezum? appeared to deliver greater improvements for IPSS and IPSS-QoL (p?<?0.001 and p?=?0.006, respectively) and lower reintervention rate (p?=?0.006) than Urolift?.

Conclusions

In this small retrospective study, our results indicate that both Rezum? and Urolift? provide a clinically significant improvement in symptoms and QoL, although some of these improvements were greater in the Rezum? arm. Future studies are needed to definitively assess which treatment would be best suited for each patient.