Recovery of metabolic impairment in patients who cleared chronic hepatitis C infection after direct-acting antiviral therapy

Chronic hepatitis C (CHC) is a complex disease that can affect different metabolic processes, including glucose and lipid metabolic pathways, with a significant impact on the development of heart disease and stroke. Recent therapy with direct-acting antivirals (DAAs), beyond its high efficacy on CHC eradication, showed a beneficial impact on glucose and lipid metabolism. This review aimed to describe current evidence regarding the association between hepatitis C virus (HCV) infection and impairment of glucose and lipid metabolism and also discusses potential public-health implications in light of the new DAA therapies and their availability at a global level. The excellent safety profile and efficacy of DAAs offer an exceptional opportunity to control the HCV pandemic at a global level and represent an opportunity for developing an operational research framework aimed at investigating the complex dynamics between host, pathogen and therapy that lead to metabolic damage in subjects with infectious diseases.     

Second cancers in MPN: Survival analysis from an international study

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A “poor prognosis” SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a “non-poor prognosis” SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.     

The Plasmodium falciparum eIK1 kinase (PfeIK1) is central for melatonin synchronization in the human malaria parasite. Melatotosil blocks melatonin action on parasite cell cycle

Melatonin and its indoles derivatives are central in the synchronization of malaria parasites. In this research, we discovered that melatonin is unable to increase the parasitemia in the human malaria Plasmodium falciparum that lacks the kinase PfeIK1. The PfeIK1 knockout strain is a valuable tool in the screening of indol-related compound that blocks the melatonin effect in wild-type (WT) parasite development. The assays were performed by using flow cytometry with simultaneous labeling for mitochondria viability with MitoTracker Deep Red and nucleus staining with SYBR Green. We found that Melatotosil leads to an increase in parasitemia in P. falciparum and blocks melatonin effect in the WT parasite. Using microscopy imaging system, we found that Melatotosil at 500 nM is able to induce cytosolic calcium rise in transgenic PfGCaMP3 parasites. On the contrary, the compound Triptiofen blocks P. falciparum cell cycle with IC₅₀ 9.76 µM ± 0.6, inhibits melatonin action, and does not lead to a cytosolic calcium rise in PfGCaMP3 parasites. We also found that the synthetic indol-related compounds arrested parasite cycle for PfeIK1 knockout and (WT) P. falciparum (3D7) in 72 hours culture assays with the IC₅₀ values slighting lower for the WT strain. We concluded that the kinase PfeIK1 is central for melatonin downstream signaling pathways involved in parasite cell cycle progression. More importantly, the indol-related compounds block its cycle as an upstream essential mechanism for parasite survival. Our data clearly show that this class of compounds emerge as an alternative for the problem of resistance with the classical antimalarials.     

The grandfather’s fever

Clinical Rheumatology - An 86-year-old Caucasian man had prior episodes of fever (up to 38 °C), mild abdominal pain, tachycardia, and malaise in the last 3 months, lasting...     

Prolonged visual reaction time after strenuous endurance exercise: higher increment in male compared to female recreational runners

Purpose

This project aimed to evaluate the simple visual reaction time (SVRT) changes in runners of both sexes before and after a 21.1 km run.

Methods

20 male (age 35.3?±?17.1 years, BMI 23.5?±?3.3 kg/m²) and 20 female (age 32.2?±?14.3 years, BMI 24.8?±?4.2 kg/m²) amateur runners were evaluated 30 min before and after a half-marathon run under competing conditions. Subjects were asked to push an electronic switch at the lighting of a lamp for 11 trials randomly divided to one another between 1 and 10 s. Effort-perception data were collected through a Borg CR100 scale and SVRT data using an electronic chronometric device. A two-way RM ANOVA assessed the effects of exercise and biological sex on SVRT.

Results

Borg effort data were similar (M: 82.4?±?3.9 vs W: 84.7?±?4.9 AU, p?=?0.68). SVRT was lower in men than women before (M: 234.05?±?3.33 vs F: 239.47?±?6.1 ms, p?<?0.05) but not after the race (M: 249.9?±?7.18 vs F: 252.09?±?16.93 ms, p?=?0.7). Exercise lengthened the SVRT (M:?+?7%; F:?+?5%; p?<?0.05). Response accuracy was greater in men both before and after exercise.

Conclusion

Previous studies suggested exercise lengthened SVRT due to an exercise intensity-related reduced post-exercise cerebral oxygenation that decreases cognitive processes efficiency. In our results, this reduction seemed higher in men. The sex-related response accuracy might be due to different estrogen effects in brain areas implicated in information processing, motor performance, and attention and to different processing and attention focus strategies between the sexes or anticipatory strategies in females.

     

Myeloid sarcoma with megakaryoblastic differentiation mimicking a sellar tumor

Myeloid sarcoma (MS) is a localized extra‐medullary tumor mass of immature myeloid cells, arising de novo or related to acute myeloid leukemia, of which it can be a forerunner, a coinciding or late event. Less commonly, MS represents an acute blastic transformation of myelodysplastic syndromes or myeloproliferative neoplasms. This rare condition commonly consists of a proliferation of more or less immature cells with a myeloid immunophenotype, very exceptional cases showing a megakaryoblastic or erythroid differentiation. The most common localization of MS is the skin, lymph node, soft tissues and bones, but CNS involvement is exceedingly rare, with no cases reported in the sellar region. We report a 54‐year‐old man, affected by myeloproliferative neoplasm, JAK2 V617F‐positive of 13 years duration, who acutely presented with a third cranial nerve palsy; neuroradiology documented a space‐occupying lesion at the level of the sellar, upper clival and right parasellar regions, that was sub‐totally removed with a trans‐sphenoidal approach. The histological examination documented a proliferation of large, blastic cells, frequently multinucleated; a diagnosis of MS with megakaryoblastic differentiation, arising in a background of chronic idiopathic myelofibrosis, was suggested by immunohistochemistry, owing to CD42b, CD45, CD61 and LAT (linker for activation of T cells) positivity. In addition, homozygous JAK2 V617F mutation was detected from the myeloid sarcoma specimen. A few weeks after surgery, an acute blastic leukemic transformation occurred and, despite chemotherapy, the patient died 2 months after surgery. To the best of our knowledge, this is the first MS case with megakaryoblastic differentiation arising within the CNS.     

The eye contact effect in request and emblematic hand gestures

Request and emblematic gestures, despite being both communicative gestures, do differ in terms of social valence. Indeed, only the former are used to initiate/maintain/terminate an actual interaction. If such a difference is at stake, a relevant social cue, i.e. eye contact, should have different impacts on the neuronal underpinnings of the two types of gesture. We measured blood oxygen level‐dependent signals, using functional magnetic resonance imaging, while participants watched videos of an actor, either blindfolded or not, performing emblems, request gestures, or meaningless control movements. A left‐lateralized network was more activated by both types of communicative gestures than by meaningless movements, regardless of the accessibility of the actor's eyes. Strikingly, when eye contact was taken into account as a factor, a right‐lateralized network was more strongly activated by emblematic gestures performed by the non‐blindfolded actor than by those performed by the blindfolded actor. Such modulation possibly reflects the integration of information conveyed by the eyes with the representation of emblems. Conversely, a wider right‐lateralized network was more strongly activated by request gestures performed by the blindfolded than by those performed by the non‐blindfolded actor. This probably reflects the effect of the conflict between the observed action and its associated contextual information, in which relevant social cues are missing.