A quantitative assessment of tremor and ataxia in FMR1 premutation carriers using CATSYS

While an established protocol exists for diagnosing individuals with the fragile X-associated tremor/ataxia syndrome (FXTAS), a quantitative measure of tremor and ataxia is needed. Using the CATSYS system to quantify movement abnormalities, we were able to record tremor, postural sway, manual (hand and finger) coordination, and reaction time in males with the FMR1 premutation, both with and without FXTAS, and compare them to controls. We evaluated 16 males diagnosed with FXTAS, 16 males with the premutation without FXTAS (non-FXTAS), and 14 age-matched controls. The CATSYS system detected, in the dominant hand, a difference in intention tremor between the FXTAS group and controls (P = 0.0008). The 30-sec postural sway tasks revealed differences between the FXTAS group and controls, both with eyes open and closed (P = 0.0004 and P = 0.0031, respectively). There was also a difference between FXTAS and non-FXTAS 30-sec postural sway performances with eyes open (P = 0.0008). The 10-sec postural sway tasks (with eyes closed) served to confirm the differences between the FXTAS group and both the controls (P = 0.0017) and non-FXTAS premutation carriers (P = 0.0016). These results demonstrate that the quantitative measures of the CATSYS system can document significant differences in intention tremor and postural sway in patients with FXTAS compared to controls.     

Different training responses to eccentric endurance exercise at low and moderate altitudes in pre-diabetic men: a pilot study

This pilot study aimed (a) to evaluate the effects of eccentric exercise training at low and moderate altitudes on physical fitness in pre-diabetic men and (b) to establish whether or not oxidative stress levels and antioxidant status were associated with performance improvements. In this crossover trial, five pre-diabetic men conducted nine downhill walking sessions (3 days/week, 3 consecutive weeks) at low altitude (from 1360 to 850 m) and one year later at moderate altitude (from 2447 to 2000 m). Exercise testing and the determination of parameters of oxidative stress and antioxidant capacity were performed pre- and post-training. The biological antioxidant activity of plasma (BAP) increased after eccentric training at moderate altitude (p < 0.001), whereas diacron reactive oxygen metabolites (dROMs) remained unchanged. Also, the BAP/dROMs ratio increased only after training at moderate-altitude training (p = 0.009). Maximum power output improved after training at low altitude and the changes were significantly related to baseline BAP/dROMs ratio (r = 0.90). No decrease was seen for fasting plasma glucose. Eccentric exercise training in pre-diabetic men improved performance only when performed at low altitude and this improvement was positively related to the baseline BAP/dROMs ratio. In contrast, 3 weeks of eccentric exercise training increased BAP levels and the BAP/dROMs ratio only at moderate altitude without improving the performance. Thus, one might speculate that the BAP/dROMs ratio has to increase before performance improvements occur at moderate altitude.

     

Electrospray fabrication of doxorubicin-chitosan-tripolyphosphate nanoparticles for delivery of doxorubicin

This work focused on a new technique for the preparation of doxorubicin (DOX) loaded chitosan (CS) nanoparticles (DOX-CS) — formation by electrospray ionization in the presence of tripolyphosphate (TPP) as the stabilizer. The working distance, needle gauge, flow rate, stirring rate, electrospraying voltage and DOX to CS molar ratio were sequentially and individually optimized and found to be a 26 gauge needle, an applied voltage of 13 kV, a flow rate of 0.5 mL/h, a working distance of 8 cm and a stirring rate of 400 rpm. The incorporation of chemically unchanged DOX with the CS into the particles was ascertained by Fourier transformed infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Under these optimized conditions, the DOX-CS particles were found to be nanoparticles of approximately 300–570 (dry particles) or 530–870 nm diameter (hydrated particles), with a PDI and SPAN polydispersity indices of 0.97–0.82 and 0.62–0.64, respectively, for initial DOX loading levels of 0.25–1%, as determined by SEM and particle size analyzer, respectively. Moreover, a high encapsulation efficiency (EE) of DOX into the nanoparticles was attained, ranging from 63.4 to 67.9% EE at 1 to 0.25% DOX loading. Finally, the in vitro DOX release behaviors of the DOX-CS particles revealed a prolonged release of DOX over at least seven hours.     

Prevalence and diversity of human rotavirus among Thai adults

Rotavirus infections have become one of the most common causes of infectious gastroenteritis in children. Although rotavirus infections have been intensively studied in infants and young children, the study in adults has been limited. As such, this study assessed the prevalence of rotaviruses and performed the molecular characterization of rotaviruses circulating in Thai adults experiencing acute gastroenteritis between January 2018 and December 2018. Group A human rotaviruses were detected in 100 feces samples by rapid immunochromatography. The peak incidence of infection occurred in February and began to decline in the summer months. From January 2018 to December 2018, there were 1344 acute gastroenteritis adult cases in the Hospital for Tropical Diseases, Bangkok, Thailand. Among these, 310 cases were rotavirus-suspected cases. Only 100 samples tested positive for rotavirus via an immunochromatography test. Twentynine out of the 100 rotavirus-positive samples were further characterized by real-time polymerase chain reaction. The G3[P8] strain was identified as the most prevalent (31.0%) followed by G1P[8], G8P[8] and G9P[8], and G2P[8], which accounted for 20.8%, 17.2%, and 13.8%, respectively. Because of the detection of rare rotavirus genotypes, such as G8, the surveillance of rotavirus epidemiology is crucial in monitoring new emergences of rotavirus strains, leading to a better understanding of the effects of strain variation for further vaccine development.     

Neuropathy as a presenting feature in fragile X-associated tremor/ataxia syndrome

Peripheral neuropathy is common among patients with fragile X-associated tremor ataxia syndrome (FXTAS). Four patients with FXTAS are described with neuropathy as the presenting feature, two having received a prior diagnosis of Charcot-Marie-Tooth (CMT) disease. A fifth is described with neuropathy as the only clinical feature. A functional connection between FXTAS and neuropathy has been suggested by the presence of lamin A/C in the intranuclear, neuronal and astrocytic inclusions of FXTAS, since mutations in lamin A/C are known to give rise to an axonal form of CMT.     

Testicular and pituitary inclusion formation in fragile X associated tremor/ataxia syndrome

PURPOSE: We describe the medical course, neuropathology and testicular pathology in 2 men who died with fragile X associated tremor/ataxia syndrome. Fragile X associated tremor/ataxia syndrome, which is a recently described, late onset neurodegenerative disorder, affects up to a third of males and occasionally females older than age 50 years who are carriers of premutation alleles (55 to 200 CGG repeats) of the fragile X mental retardation 1 gene FMR1. Clinical manifestations of premutation status are distinct from those of the full mutation, which is the cause of the fragile X syndrome. MATERIALS AND METHODS: Standard pathological techniques were used to examine the brain, pituitary gland and testicular tissues of 2 males who had fragile X associated tremor/ataxia syndrome. RESULTS: The clinical course of the 2 cases included impotence before the onset of neurological symptoms of tremor and ataxia. Neuropathological findings included eosinophilic intranuclear inclusions in neurons and astrocytes throughout the central nervous system, and in the anterior and posterior pituitary gland of 1 of the 2 men. Inclusions were also seen in the Leydig and myoid cells in the testicles of these 2 men with fragile X associated tremor/ataxia syndrome. CONCLUSIONS: Fragile X associated tremor/ataxia syndrome inclusions are formed in tissues outside of the central nervous system. Involvement of the testicles and the pituitary gland may lead to neuroendocrine dysfunction, including testosterone deficiency. These noncentral nervous system components of fragile X associated tremor/ataxia syndrome require further study.     

Molecular Characterization of Seasonal Influenza A and B from Hospitalized Patients in Thailand in 2018–2019

Influenza viruses continue to be a major public health threat due to the possible emergence of more virulent influenza virus strains resulting from dynamic changes in virus adaptability, consequent of functional mutations and antigenic drift in surface proteins, especially hemagglutinin (HA) and neuraminidase (NA). In this study, we describe the genetic and evolutionary characteristics of H1N1, H3N2, and influenza B strains detected in severe cases of seasonal influenza in Thailand from 2018 to 2019. We genetically characterized seven A/H1N1 isolates, seven A/H3N2 isolates, and six influenza B isolates. Five of the seven A/H1N1 viruses were found to belong to clade 6B.1 and were antigenically similar to A/Switzerland/3330/2017 (H1N1), whereas two isolates belonged to clade 6B.1A1 and clustered with A/Brisbane/02/2018 (H1N1). Interestingly, we observed additional mutations at antigenic sites (S91R, S181T, T202I) as well as a unique mutation at a receptor binding site (S200P). Three-dimensional (3D) protein structure analysis of hemagglutinin protein reveals that this unique mutation may lead to the altered binding of the HA protein to a sialic acid receptor. A/H3N2 isolates were found to belong to clade 3C.2a2 and 3C.2a1b, clustering with A/Switzerland/8060/2017 (H3N2) and A/South Australia/34/2019 (H3N2), respectively. Amino acid sequence analysis revealed 10 mutations at antigenic sites including T144A/I, T151K, Q213R, S214P, T176K, D69N, Q277R, N137K, N187K, and E78K/G. All influenza B isolates in this study belong to the Victoria lineage. Five out of six isolates belong to clade 1A3-DEL, which relate closely to B/Washington/02/2009, with one isolate lacking the three amino acid deletion on the HA segment at position K162, N163, and D164. In comparison to the B/Colorado/06/2017, which is the representative of influenza B Victoria lineage vaccine strain, these substitutions include G129D, G133R, K136E, and V180R for HA protein. Importantly, the susceptibility to oseltamivir of influenza B isolates, but not A/H1N1 and A/H3N2 isolates, were reduced as assessed by the phenotypic assay. This study demonstrates the importance of monitoring genetic variation in influenza viruses regarding how acquired mutations could be associated with an improved adaptability for efficient transmission.