Covid-19 and Parkinson's disease: an overview.

In March 2020, WHO declared Covid-19 outbreak pandemic. There has been increasing evidence that frail, old, multi-pathological patients are at greater risk of developing severe Covid-19 infection than younger, healthy ones. Covid-19's impact on Parkinson's Disease (PD) patients could be analysed through both the influence on PD patients' health and their risk of developing severe Covid-19, and the consequences of lockdown and restrictive measures on mental and cognitive health on both patients and caregivers. Moreover, there are critical issues to be considered about patients' care and management through an unprecedented time like this. One important issue to consider is physiotherapy, as most patients cannot keep exercising because of restrictive measures which has profoundly impacted on their health. Lastly, the relationship between PD and Sars-Cov2 may be even more complicated than it seems as some studies have hypothesized a possible Covid-19-induced parkinsonism. Hereby, we review the state of the art about the relationship between Covid-19 and Parkinson's Disease, focusing on each of these five points.

Rhinogenic and sinus headache - Literature review.

BACKGROUND: Headache is a common, yet challenging symptom to evaluate given its wide range of clinical presentations and different etiologies. For centuries, conceptual understanding of headache causation has been attributed to anatomic abnormalities of the nose and paranasal sinuses. METHODS: Structured literature review. RESULTS: The number of cases, categorized as migraines or other primary headaches, misdiagnosed as a "sinus headache" is high in the literature, ranging from 50 to 80%. The potential mechanisms for rhinogenic headaches were classically described as pain secondary to prolonged mucosal contact points, hypoxia in the paranasal sinuses secondary to poor ventilation, or pressure caused by the growth of nasal polyps. Additionally, other mechanisms were described and are still being studied. Corrective surgery for mucosal contact points in the nasal cavity is deemed necessary for relieving the headache, although patient outcomes are variable. CONCLUSION: Delay in proper diagnosis and treatment negatively impact patient quality of life. Most cases of "sinus headache" or "rhinogenic headache" seen in clinical practice are in fact misdiagnosed as either primary headaches or migraines. Because of increased misdiagnoses, Otolaryngologists should establish a direct and precise diagnosis congruent with a chief complaint being a headache. Vital information such as a good clinical history, well-performed nasal endoscopy, and occasional CT scan may decrease misdiagnosis probability.

Low-intensity repetitive paired associative stimulation targeting the motor hand area at theta frequency causes a lasting reduction in corticospinal excitability.

OBJECTIVE: Sub-motor threshold 5 Hz repetitive paired associative stimulation (5 Hz-rPAS25ms) produces a long-lasting increase in corticospinal excitability. Assuming a spike-timing dependent plasticity-like (STDP-like) mechanism, we hypothesized that 5 Hz-rPAS at a shorter inter-stimulus interval (ISI) of 15 ms (5 Hz-rPAS15ms) would exert a lasting inhibitory effect on corticospinal excitability. METHODS: 20 healthy volunteers received two minutes of 5 Hz-rPAS15ms. Transcranial magnetic stimulation (TMS) was applied over the motor hotspot of the right abductor pollicis brevis muscle at 90% active motor threshold. Sub-motor threshold peripheral electrical stimulation was given to the left median nerve 15 ms before each TMS pulse. We assessed changes in mean amplitude of the unconditioned motor evoked potential (MEP), short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and cortical silent period (CSP) before and for 60 minutes after 5-Hz rPAS15ms. RESULTS: Subthreshold 5-Hz rPAS15ms produced a 20-40% decrease in mean MEP amplitude along with an attenuation in SAI, lasting at least 60 minutes. A follow-up experiment revealed that MEP facilitation was spatially restricted to the target muscle. CONCLUSIONS: Subthreshold 5-Hz rPAS15ms effectively suppresses corticospinal excitability. Together with the facilitatory effects of subthreshold 5-Hz rPAS25ms (Quartarone et al., J Physiol 2006;575:657-670), the results show that sub-motor threshold 5-Hz rPAS induces STDP-like bidirectional plasticity in the motor cortex. SIGNIFICANCE: The results of the present study provide a new short-time paradigm of long term depression (LTD) induction in human sensory-motor cortex.

Pneumomediastinum following intubation in COVID-19 patients: a case series.

The number of patients requiring tracheal intubation rose dramatically in March and April 2020 with the COVID-19 outbreak. Our thoracic surgery department has seen an increased incidence of severe pneumomediastinum referred for surgical opinion in intubated patients with COVID-19 pneumonitis. Here we present a series of five patients with severe pneumomediastinum requiring decompression therapy over a 7-day period in the current COVID-19 outbreak. We hypothesise that the mechanism for this is the aggressive disease pathophysiology with an increased risk of alveolar damage and tracheobronchial injury, along with the use of larger-bore tracheal tubes and higher ventilation pressures. We present this case series in order to highlight the increased risk of this potentially life-threatening complication among the COVID-19 patient cohort and offer guidance for its management to critical care physicians.

A virtuous diagnostic and therapeutic roadmap triggered by a motivated and skilful urinary sediment examination.

In this paper we describe how an accurate urinary sediment examination, which revealed the presence of a severe 2,8-dihydroxyadenine crystalluria, opened the way to an articulate and successful diagnostic and therapeutic roadmap for a rare and potentially severe renal disease.

Parathyroid scintigraphy in primary hyperparathyroidism: comparison between double-phase and subtraction techniques and possible affecting factors.

PURPOSE: Parathyroid scintigraphy is superior to other imaging techniques in detecting hyperfunctioning parathyroid glands. It is mainly performed using double-phase or dual-tracer subtraction methods. Neither of the techniques is perfect and different protocols are being used. We aimed to evaluate the accuracy of double-phase and subtraction methods in detecting abnormal gland as well as the potential effects of coexisting thyroid disease and clinical-laboratory data. METHODS: We considered patients with primary hyperparathyroidism who underwent parathyroid surgery, after a parathyroid scintigraphy between April 2015 and February 2017. Sixty-eight patients were included; in 45 cases (66.2%), a thyroid disease was coexistent. Diagnostic performances of the two techniques were compared. The effect of thyroid disease and clinical-pathological data on examination interpretation was considered. RESULTS: Double-phase scintigraphy showed higher sensitivity and accuracy in detecting the exact abnormal gland compared to the digital subtraction (90% and 75% vs. 76% and 66%, respectively). For double-phase technique, sensitivity and accuracy were higher in cases with no thyroid disease when compared to those with thyroid disease (92% and 86% vs. 88% and 69%, respectively). Similarly, for digital subtraction, sensitivity and accuracy were higher in the absence of thyroid disease compared to their presence (84% and 79% vs. 70% and 58%, respectively). There was no significant variation in the performance of both techniques, considering clinical-laboratory data. CONCLUSIONS: Double-phase scintigraphy has been more accurate than digital subtraction. The presence of thyroid disease could be a possible limit, affecting the subtraction more than the double-phase technique. Clinical data did not influence the scintigraphic outcome.

Spatial Integration of Somatosensory Inputs during Sensory-Motor Plasticity Phenomena Is Normal in Focal Hand Dystonia.

Background: Surround inhibition is a system that sharpens sensation by creating an inhibitory zone around the central core of activation. In the motor system, this mechanism probably contributes to the selection of voluntary movements, and it seems to be lost in dystonia. Objectives. To explore if sensory information is abnormally processed and integrated in focal hand dystonia (FHD) and if surround inhibition phenomena are operating during sensory-motor plasticity and somatosensory integration in normal humans and in patients with FHD. Methods. We looked at the MEP facilitation obtained after 5 Hz repetitive paired associative stimulation of median (PAS M), ulnar (PAS U), and median + ulnar nerve (PAS MU) stimulation in 8 normal subjects and 8 FHD. We evaluated the ratio MU/(M + U) ∗ 100 and the spatial and temporal somatosensory integration recording the somatosensory evoked potentials (SEPs) evoked by a dual nerve input. Results: FHD had two main abnormalities: first, the amount of facilitation was larger than normal subjects; second, the spatial specificity was lost. The MU/(M + U) ∗ 100 ratio was similar in healthy subjects and in FHD patients, and the somatosensory integration was normal in this subset of patients. Conclusions. The inhibitory integration of somatosensory inputs and the somatosensory inhibition are normal in patients with focal dystonia as well as lateral surrounding inhibition phenomena during sensory-motor plasticity in FHD.

Glioblastoma del nervio óptico detectado por PET/TC cerebral con 11C-Metionina / Optic nerve glioblastoma detected by 11C-Methionine brain PET/CT

No disponible

Effects of Toceranib Phosphate on the Hypothalamic-Pituitary-Thyroid Axis in Tumor-Bearing Dogs.

BACKGROUND: Thyroid dysfunction is associated with the use of tyrosine kinase inhibitors (TKI) in people. HYPOTHESIS/OBJECTIVES: To determine whether dysfunction in the hypothalamic-pituitary-thyroid axis occurs in dogs receiving the TKI, toceranib phosphate. ANIMALS: Forty-three client-owned dogs with cancer. METHODS: Prospective, observational study. Concentrations of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), and thyroid-stimulating hormone (TSH) were evaluated on day 0, 30, and 90. Dogs also were evaluated for the presence of thyroglobulin autoantibodies. RESULTS: The proportion of dogs with low TT4, low FT4, low TT3, high TSH, or primary hypothyroidism (increased TSH and decreased TT4, FT4 or both) did not change over 90 days. Hormone concentrations remained within laboratory reference intervals, but FT4 (P = 0.0032) and TSH (P < 0.0001) changed over time. Mean FT4 was 1.22 ng/dL (95% confidence interval [CI], 1.10-1.34) on day 0 and 1.00 ng/dL (95% CI, 0.86-1.16) on day 90. Mean TSH was 0.17 ng/mL (95% CI, 0.13-0.23) on day 0 and 0.34 ng/mL (95% CI, 0.24-0.48) on day 90. Furthermore, TT4/TT3 ratio also changed over time (P = 0.0086). Mean TT4/TT3 ratio was 2.57 (95% CI, 2.26-2.88) on day 0 and 2.02 on day 90 (95% CI, 1.61-2.44). Thyroglobulin autoantibodies were not detected in any dog. CONCLUSIONS AND CLINICAL IMPORTANCE: Toceranib phosphate can disrupt the hypothalamic-pituitary-thyroid axis in dogs. Periodic evaluation of TT4, FT4, TT3, and TSH should be carried out in dogs receiving long-term treatment with this medication.

Stabilization vs. destabilization of G-quadruplex superstructures: the role of the porphyrin derivative having spermine arms.

The interaction of the porphyrin derivative H2TCPPSpm4, having spermine pendants in the four meso positions, with the G-quadruplex (GQ) structure formed by the DNA aptamer TGGGAG has been investigated by means of UV, electronic circular dichroism and PAGE studies. The results reported here demonstrate that the porphyrin derivative is capable of stabilizing or destabilizing the higher-ordered structures of parallel GQs, depending on the method used to reach their relative stoichiometry (titration vs. single addition). Noteworthily, when two equivalents of H2TCPPSpm4 were mixed directly with one equivalent of the (TGGGAG)4 GQ to reach a 2 : 1 H2TCPPSpm4 : GQ ratio T1/2 higher than 80 °C was also observed confirming the presence of higher-ordered GQ structures.

The effects of sulforaphane on canine osteosarcoma proliferation and invasion.

Recent evidence in in vitro and in vivo models suggests that sulforaphane (SFN), found in raw cruciferous vegetables, may have utility in chemoprevention, as an antineoplastic agent and as a free radical scavenger. The effects of SFN alone or with doxorubicin on cell viability were examined, as well as cell cycle kinetics, invasion capabilities and apoptosis in three canine osteosarcoma cell line (D17, OS 2.4 and HMPOS). Results showed that SFN could not induce cell death at potentially physiological concentrations (<50 µM), but significantly diminished cell invasion and downregulation of focal adhesion kinase (FAK) signaling. Modest cell cycle changes were observed in each cell line. When doxorubicin was used in conjunction with SFN, there was a protective effect to doxorubicin-induced cytotoxicity in D17 and OS 2.4 cells. Further studies examining SFN as a supplement are warranted, particularly in light of pro-proliferative and cytoprotective properties in canine osteosarcoma.

The use, publication and future directions of immunocytochemistry in veterinary medicine: a consensus of the Oncology-Pathology Working Group.

One of the primary objectives of the Oncology Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this document, the authors provide descriptions of the literature reviewed, the review process, and a summary of the information gathered on immunocytochemistry. The intent of this publication is to help educate practitioners and pathologists on the process of immunocytochemistry and to provide a guide for the use of this technique in veterinary medicine. This document represents the opinions of the working group and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society.

DJ-1 modulates mitochondrial response to oxidative stress: clues from a novel diagnosis of PARK7.

DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2% of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c.461C>A [p.T154K] mutation in DJ-1. Patient's cultured fibroblasts showed low ATP synthesis, high ROS levels and reduced amount of some subunits of mitochondrial complex I; biomarkers of oxidative stress also resulted abnormal in patient's blood. The clinical pattern of multisystem involvement and the biochemical findings in our patient highlight the role for DJ-1 in modulating mitochondrial response against oxidative stress.

Cortical excitability in patients with resistance to thyroid hormone compared to patients with hypothyroidism and euthyroid controls: a transcranial magnetic stimulation study.

Resistance to thyroid hormone (RTH) describes a rare syndrome in which serum levels of thyroid hormones are elevated but serum levels of thyroid stimulating hormone (TSH) are unsuppressed. The importance of thyroid hormones for the normal function of the adult brain is corroborated by the frequent association of thyroid dysfunctions with neurological and psychiatric symptoms. In this study we investigated whether adult thyroid hormone resistance affects cortical excitability and modulates inhibitory and excitatory intracortical circuitries by using transcranial magnetic stimulation. Cortical excitability was probed with transcranial magnetic stimulation in 4 patients with thyroid hormone resistance, 10 patients affected by overt hypothyroidism (OH) and 10 age-matched healthy controls. We tested motor thresholds, motor evoked potential recruitment curve, cortical silent period (CSP), short interval intracortical inhibition (SICI) and intracortical facilitation. In both OH and RTH patients, the inhibitory cortical circuits were affected compared with euthyroid controls, but in opposite ways. In OH patients, CSP was prolonged and SICI was decreased. On the contrary, in RTH patients CSP was shortened and SICI was increased. Thyroid hormones may influence cortical excitability and cortical inhibitory circuits.

Response of colonic motility to dopaminergic stimulation is subverted in rats with nigrostriatal lesion: relevance to gastrointestinal dysfunctions in Parkinson's disease.

BACKGROUND: Constipation is extremely common in patients with Parkinson's disease (PD) and has been described in PD animal models. In this study, we investigated whether a PD-like degeneration of dopaminergic neurons of the substantia nigra can influence peristalsis in colonic segments of rats by impacting on enteric dopaminergic transmission. METHODS: Male, Sprague-Dawley rats received a unilateral injection of neurotoxin 6-hydroxydopamine (6-OHDA), or saline, into the medial-forebrain-bundle. Peristaltic activity was recorded in isolated colonic segments, in baseline conditions and following exposure to combinations of D2 receptor (DRD2) agonist sumanirole and antagonist L-741626. Dopamine levels and DRD2 expression were assessed in the ileum and colon of animals. We also investigated the involvement of the dorsal motor nucleus of the vagus (DMV) - a potential relay station between central dopaminergic denervation and gastrointestinal (GI) dysfunction - by analyzing cytochrome c oxidase activity and FosB/DeltaFosB expression in DMV neurons. KEY RESULTS: We observed profound alterations in the response of colonic segments of 6-OHDA lesioned animals to DRD2 stimulation. In fact, the inhibition of colonic peristalsis elicited by sumanirole in control rats was absent in 6-OHDA-lesioned animals. These animals also showed reduced DRD2 expression in the colon, along with elevation of dopamine levels. No significant changes were detected within the DMV. CONCLUSIONS & INFERENCES: Our results demonstrate that selective lesion of the nigrostriatal dopaminergic pathway subverts the physiological response of the colon to dopaminergic stimulation, opening new perspectives in the comprehension and treatment of GI dysfunctions associated with PD.

Cannabinoid and nitric oxide signaling interplay in the modulation of hippocampal hyperexcitability: Study on electrophysiological and behavioral models of temporal lobe epilepsy in the rat.

A growing bulk of evidence suggests that cannabinoid system plays a pivotal role in the control of hyperexcitability phenomena. Notwithstanding, the anticonvulsant action of cannabinoids has not been fully addressed, in particular the involvement of potential cellular neuromodulators, for instance nitric oxide. In the current study, we focused on two distinct rat models of temporal lobe epilepsy, the Maximal Dentate Activation and the pilocarpine-induced acute seizures, providing both electrophysiological and behavioral data on cannabinoid and nitrergic system interplay. We evaluated the antiepileptic effects of WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), a CB agonist, and of 7-Nitroindazole (7NI), a preferential neuronal nitric oxide synthase (nNOS) inhibitor, at different doses, alone and in combination. MDA study showed that these drugs protected animals in a dose-dependent manner from electrically induced epileptiform discharges. In pilocarpine model, a dose-related activity of 7NI and WIN: a) decreased the behavioral scoring, used to describe the severity of chemically induced acute seizures; b) affected latency of the onset of acute convulsions; c) dampened mortality rate. Interestingly, the combination of the treatments brought to light that individually ineffective doses of WIN turn into effective when nNOS activity is pharmacologically inhibited in both experimental conditions. This effect is mediated by CB1 receptor since the co-administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), a CB1 receptor specific antagonist, thwarted the 7NI-WIN convergent action. In the light of this, our findings suggest a putative antagonism between CBr-activated pathway and NO signaling in the context of neuronal hyperexcitability and contribute to elucidate possible synaptic processes underlying neuroprotective properties of cannabinoids, with a view to better integrate antiepileptic therapy.

A new species of Troglocharinus Reitter, 1908 (Coleoptera, Leiodidae, Cholevinae, Leptodirini) from southern Catalonia, with a molecular phylogeny of the related species group.

In this paper we describe T. pallisei sp. n., a new representative of the genus Troglocharinus Reitter, 1908 (Coleoptera, Leiodidae, Leptodirini), a strictly subterranean genus restricted to the Eastern Pyrenees and some coastal areas in Catalonia. All known specimens of T. pallisei sp. n. were collected in a cave next to the town of La Riba, in the province of Tarragona (Spain), situated between the distribution areas of the species of the T. orcinus complex and T. espanoli Jeannel, 1930. It can be separated from the other members of the T. orcinus complex by the presence of penicillus in the apex of the parameres of the aedeagus and from T. espanoli by the presence of a mesoventral keel; it also differs from both by its long and erect pubescence. A Bayesian molecular phylogeny including representatives of the main lineages within the genus Troglocharinus, based on ca. 5211 Kb of 5 mitochondrial and 4 nuclear genes, placed T. pallisei sp. n. as sister to T. orcinus Jeannel, 1910, and both sister to T. espanoli, in perfect agreement with their geographic distributions and the inferred geographic expansion of the genus to the south, with an estimated divergence of ca. 1.3 Ma. In agreement with the results of a previous phylogenetic study, the subgenus Antrocharidius Jeannel, 1910 is synonymised with Troglocharinus (syn.n.).

Changes in extra- and intracellular pH in hepatocytes exposed to gabexate mesilate.

Gabexate mesilate (GM) is a synthetic inhibitor of plasmatic and pancreatic serine proteases licensed for the treatment of pancreatitis. Here we show that in suspensions of isolated hepatocytes, profound changes in extracellular, cytoplasmic, and vesicular pH occur after addition of GM. Isolated hepatocytes obtained by collagenase perfusion of rat liver were pre-incubated with 1, 2, and 4 mM GM. Extracellular pH (pH in the incubation medium) was measured by a conventional pH electrode, cytosolic and vesicular pH were measured by fluorescence changes of 2',7'-biscarboxyethyl-5,6-carboxyfluorescein acetoxymethyl ester (BCECF-AM) and fluorescein dextran, respectively. Incubation of hepatocytes with GM resulted in a dose-dependent decrease of extracellular pH. Cytosolic pH decreased rapidly and markedly in a dose-dependent manner during the first minutes and gradually returned towards baseline. Simultaneously, GM induced a rapid alkalinization of acidic vesicles. The presence of bis-(p-nitrophelyl) phosphate (BNPP), an esterase inhibitor, reduced the extent of extracellular acidification. Incubation of hepatocytes in the presence of dimethylamiloride, an Na+/H+ exchanger inhibitor, or in a sodium-free medium, did not modify the rate and extent of extracellular acidification. GM, a commercially available pharmacological agent, could be useful to manipulate extra- and intracellular pH.

Severe polymyositis due to Toxoplasma gondii in an adult immunocompetent patient: a case report and review of the literature.

Toxoplasmosis, a worldwide zoonosis caused by a coccidian parasite Toxoplasma gondii, is more often asymptomatic in immunocompetent patients. We report the case of a 38-year-old immunocompetent male with a polymyositis as the presenting manifestation of T. gondii infection. The patient was hospitalized for a 30-day history of fever (T max 39.5°C), muscle pain, and progressive weakness of the muscles. A diagnosis of polymyositis was made, and he was started on corticosteroid treatment, which caused no reduction of symptoms. After finding a positive polymerase chain reaction (PCR) assay for T. gondii, together with additional clinical findings, a diagnosis of acute toxoplasmosis was made. Specific treatment with pyrimethamine and sulfadiazine was started, with a progressive reduction of symptoms and normalization of laboratory tests.