Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Minocycline Improves Memory by Enhancing Hippocampal Synaptic Plasticity and Restoring Antioxidant Enzyme Activity in a Rat Model of Cerebral Ischemia-Reperfusion.

Introduction: Oxidative stress plays a crucial role in the impairment of synaptic plasticity following cerebral ischemia, ultimately resulting in memory dysfunction. Hence, the applying antioxidant agents could be beneficial in managing memory deficits after brain ischemia. Minocycline is a tetracycline antibiotic with antioxidant effect. The main objective of this work was to assess the minocycline effect on the impairment of synaptic plasticity and memory after cerebral ischemia-reperfusion in rats. Methods: Transient occlusion of common carotid arteries was used to induce ischemiareperfusion injury in rats. Single or multiple (once daily for 7 days) dose(s) of minocycline were administered before (pretreatment) or after (treatment) brain ischemia. Seven days after ischemia-reperfusion, passive avoidance performance, long-term hippocampal potentiation, and the activity of antioxidant enzymes were assessed. Results: The passive avoidance test showed that minocycline (20 and 40 mg/kg) significantly increased step-through latency while reducing the duration of staying in a dark chamber in the treatment (but not pretreatment) group. In electrophysiological experiments, the rats treated (but not pretreated) with minocycline (40 mg/kg) showed a significant increase in the amplitude of the field excitatory postsynaptic potentials in the dentate gyrus area of the hippocampus. The treatment (but not pretreatment) with minocycline (20 and 40 mg/kg) resulted in a significant increase in the activity of catalase, glutathione peroxidase, and superoxide dismutase in the hippocampus. Conclusion: It was determined that minocycline attenuates memory dysfunction after cerebral ischemia-reperfusion in rats by improving hippocampal synaptic plasticity and restoring antioxidant enzyme activity. Highlights: Minocycline enhances passive avoidance memory after cerebral ischemia-reperfusion.Minocycline increases enzymatic antioxidant capacity in hippocampal formation.Minocycline improves synaptic plasticity in perforant path-granule cell synapse. Plain Language Summary: Stroke is a common neurological disease with a relatively high mortality rate and disabilities worldwide. More than half of the patients who have had an episode of stroke suffer from the impairment of sensorimotor function and language problems as well as learning and memory disorders. Oxidative stress plays an important role in memory impairment following brain ischemia. Hence, the application of antioxidant agents could be beneficial in managing memory deficits after stroke. Minocycline is a tetracycline antibiotic that is used for the treatment of infectious diseases; it can also function as a potent antioxidant medication. Hence, we hypothesized that minocycline could attenuate memory impairment after brain ischemia. We examined this hypothesis in a rat model of brain ischemia. In this model, the main arteries that supply the brain with oxygenated blood were occluded to induce brain ischemia in the rats. Then, minocycline was administered to the rats, which were subjected to brain ischemia. Seven days later, memory function in the rats was evaluated. The results showed that minocycline could enhance the activity of antioxidant enzymes in the brain, which physiologically fight off oxidative stress. This property of minocycline protects brain cells against ischemic injury and thereby increases the transmission of neuronal signals from one cell to another cell in the memory centers in the brain. These effects ultimately increase the memory function of rats, which was evident in the behavioral memory test. Overall, the study results suggest that minocycline can be considered a memory enhancer drug in patients who suffer from learning and memory disorders following a stroke.

Attenuating effect of paroxetine on memory impairment following cerebral ischemia-reperfusion injury in rat: The involvement of BDNF and antioxidant capacity.

Memory impairments are frequently reported in patients suffering from brain ischemic diseases. Oxidative/nitrosative stress, synaptic plasticity, and brain-derived neurotrophic factor (BDNF) are involved in the physiopathology of brain ischemia-induced memory disorders. In the present study, the effect of paroxetine as an efficacious antidepressant medication with antioxidant properties was evaluated on passive avoidance memory deficit following cerebral ischemia in rats. Transient occlusion of common carotid arteries was applied to induce ischemia-reperfusion injury in male Wistar rats. Paroxetine (5, 10, 20 mg/kg) was administered intraperitoneally once daily before (for 3 days) or after (for 7 days) the induction of ischemia. A week after ischemia-reperfusion injury, passive avoidance memory, long-term potentiation (LTP), BDNF levels, total antioxidant capacity, the activity of antioxidant enzymes (including catalase, glutathione peroxidase, and superoxide dismutase), the concentration of malondialdehyde (MDA), and nitric oxide (NO) were investigated in the hippocampus. In the passive avoidance test, paroxetine significantly increased the step-through latency and decreased the time spent in the dark compartment. This affirmative function of paroxetine on the passive avoidance memory was accompanied by the improvement of hippocampal LTP and an obvious augmentation in the BDNF contents. Besides, paroxetine caused a significant rise in the total antioxidant capacity and antioxidant enzyme activity; while decreased the hippocampal levels of NO and MDA. It was ultimately attained that paroxetine attenuates cerebral ischemia-induced passive avoidance memory dysfunction in rats by the enhancement of hippocampal synaptic plasticity and BDNF content together with the suppression of oxidative/nitrosative stress.

A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations.

In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.