A rare case of adult-onset spastic paraparesis associated with Klinefelter syndrome.

REPORT: The rare association of Klinefelter syndrome and the clinical presentation of a late onset chronic progressive spastic paresis. CLINICAL PRESENTATION AND GENETICS: An infertile, 61-year-old man, presented with late adult onset of gait problems, deep muscle pain, and bladder problems. He presented for the first time, years after onset with a spastic paraparesis with high arched feet. His parents had already died, but the patient described high arched feet with his mother. There is no further certain information about the parents. After thorough investigation, an additional X chromosome was found, whereafter the diagnosis of Klinefelter syndrome could be made. Other acquired and genetic causes for spastic paraparesis or hereditary motor neuropathy are excluded. CONCLUSION: This rare case, together with three other literature reports by Sasaki (Intern Med 58(3):437-440, 2019), Sajra (Med Arh 61(1):52-53, 2007) and Matsubara et al., (J Neurol Neurosurg Psychiatry 57(5):640-642, 1994). suggests that Klinefelter syndrome can be associated with spastic paraparesis, besides the other various neuropsychiatric symptoms that are more commonly described.

Bridging: Accelerating Regulatory Acceptance of Reduced-Risk Tobacco and Nicotine Products.

INTRODUCTION: The number and variety of alternative tobacco and nicotine products that can potentially provide reduced-risk choices for cigarette smokers who switch completely to such products instead of continued smoking have grown substantially in the past decade. Innovation and choice are likely to improve the prospects of smokers making the switch, but this provides challenges to regulators and manufacturers to ensure that changes to regulations and products promote and do not hinder contributions to tobacco harm reduction. AIMS AND METHODS: This paper looks at where bridging data sets for tobacco heating products, closed system vaping products, and oral nicotine products might enable innovation while protecting the interests of consumers. RESULTS: We review product data from chemical studies and a toxicological study showing how bridging can be applied and consider what product development changes might allow bridging from existing datasets or trigger the need for new ones. CONCLUSIONS: Bridging across specific product ranges can increase the speed of innovation, foster competition, and limit the burden of assessment for regulators while maintaining product safety and quality. IMPLICATIONS: Bridging partial data sets is an established practice within other industries, that aims to improve efficiency with regulatory approvals, accepts natural product variation, and supports product innovation. We review product data from chemical studies and a toxicological study showing how bridging can be applied and consider what product development changes might allow bridging from existing datasets or trigger the need for new ones. This in turn can increase the speed of innovation, foster competition, and limit the burden of assessment for regulators while maintaining product safety and quality.

A Single Bolus of Docosahexaenoic Acid Promotes Neuroplastic Changes in the Innervation of Spinal Cord Interneurons and Motor Neurons and Improves Functional Recovery after Spinal Cord Injury.

Docosahexaenoic acid (DHA) is an ω-3 polyunsaturated fatty acid that is essential in brain development and has structural and signaling roles. Acute DHA administration is neuroprotective and promotes functional recovery in animal models of adult spinal cord injury (SCI). However, the mechanisms underlying this recovery have not been fully characterized. Here we investigated the effects of an acute intravenous bolus of DHA delivered after SCI and characterized DHA-induced neuroplasticity within the adult injured spinal cord. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat cervical hemisection SCI model. A mouse pyramidotomy model was used to confirm that this robust sprouting was not species or injury model specific. Furthermore, we demonstrated that corticospinal fibers sprouting to the denervated side of the cord following pyramidotomy contact V2a interneurons. We also demonstrated increased serotonin fibers and synaptophysin in direct contact with motor neurons. DHA also increased synaptophysin in rat cortical cell cultures. A reduction in phosphatase and tensin homolog (PTEN) has been shown to be involved in axonal regeneration and synaptic plasticity. We showed that DHA significantly upregulates miR-21 and downregulates PTEN in corticospinal neurons. Downregulation of PTEN and upregulation of phosphorylated AKT by DHA were also seen in primary cortical neuron cultures and were accompanied by increased neurite outgrowth. In summary, acute DHA induces anatomical and synaptic plasticity in adult injured spinal cord. This study shows that DHA has therapeutic potential in cervical SCI and provides evidence that DHA could exert its beneficial effects in SCI via enhancement of neuroplasticity. SIGNIFICANCE STATEMENT: In this study, we show that an acute intravenous injection of docosahexaenoic acid (DHA) 30 min after spinal cord injury induces neuroplasticity. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat hemisection spinal cord injury model. A mouse pyramidotomy model was used to confirm that the robust sprouting involved V2a interneurons. We show that DHA significantly upregulates miR-21 and phosphorylated AKT, and downregulates phosphatase and tensin homolog (PTEN), which is involved in suppressing anatomical plasticity, in corticospinal neurons and in primary cortical neuron cultures. We conclude that acute DHA can induce anatomical and synaptic plasticity. This provides direct evidence that DHA could exert its beneficial effects in spinal cord injury via neuroplasticity enhancement.

Effect of body mass and activity on the metabolic rate and ammonia-N excretion of the spiny lobster Sagmariasus verreauxi during ontogeny.

Intraspecific analyses of the relationship between metabolic rate and mass have rarely been considered during complete ontogeny. Spiny lobsters are fascinating candidates to examine metabolic changes during ontogeny because their life cycle includes an extended planktonic, nektonic, and benthic life stages. The effect of body mass on metabolic rates, aerobic scope, and ammonia-N excretion of Sagmariasus verreauxi juveniles were examined to determine energetic demands through juvenile development. Mass-independent routine oxygen consumption increased allometrically during juvenile development with a mass scaling exponent of 0.83. The mass scaling exponent of active metabolism (0.81) was reduced compared to standard metabolism (0.91) of juvenile lobsters. The aerobic scope of juvenile lobsters decreased with larger body mass. To examine if the mass scaling exponent varies with ontogeny, we compared our data with previous measurements made with larvae of the same species. Comparison between mass scaling exponents showed they were higher for phyllosoma (0.97) compared to juvenile (0.83) development. Higher scaling exponents for phyllosoma may be attributed to increased growth rates of phyllosoma compared to juveniles, which increase oxygen consumption due to the higher energy cost of growth. The mass scaling exponent for complete ontogeny (0.91) of S. verreauxi was larger than the commonly cited 0.67 (1/3) and 0.75 (3/4) mass scaling exponents, indicating that species-specific differences can be a large factor affecting allometric relationships of animals.

Drivers of medicalization in the Canadian Adult Obesity Clinical Practice Guidelines.

The new Canadian Adult Obesity Clinical Practice Guidelines frame higher body weight as a chronic, relapsing disease requiring comprehensive medical treatment pathways. In this commentary, we will demonstrate how a process called pharmaceuticalization is informing the new guidelines. We join those questioning the normalization of industry and medical collaboration and interrogate whether the new guidelines meaningfully address stigma.

RéSUMé: Les nouvelles Lignes directrices canadiennes de pratique clinique de l'obésité chez l'adulte présentent le poids corporel élevé comme une maladie chronique récurrente nécessitant un parcours de soins médicaux complet. Dans notre commentaire, nous montrerons que ces nouvelles lignes directrices sont éclairées par un processus de « pharmaceuticalisation ¼. Nous joignons notre voix aux personnes qui remettent en question la normalisation de la collaboration entre l'industrie et la médecine, et nous nous demandons si les nouvelles lignes directrices abordent utilement la stigmatisation.

Ingested plastic and trace element concentrations in Short-tailed Shearwaters (Ardenna tenuirostris).

Pollution of marine environments is concerning for complex trophic systems. Two anthropogenic stresses associated with marine pollution are the introduction of marine plastic and their associated chemicals (e.g., trace elements) which, when ingested, may cause harm to wildlife. Here we explore the relationship between plastic ingestion and trace element burden in the breast muscle of Short-tailed Shearwaters (Ardenna tenuirostris). We found no relationship between the amount of plastic ingested and trace element concentration in the birds' tissues. Though the mass and number of plastic items ingested by birds during 1969-2017 did not change significantly, trace element concentrations of some elements (Cu, Zn, As, Rb, Sr and Cd), appeared to have increased in birds sampled in 2017 compared to limited data from prior studies. We encourage policy which considers the data gleaned from this sentinel species to monitor the anthropogenic alteration of the marine environment.

Uncovering the sub-lethal impacts of plastic ingestion by shearwaters using fatty acid analysis.

Marine plastic pollution is increasing exponentially, impacting an expanding number of taxa each year across all trophic levels. Of all bird groups, seabirds display the highest plastic ingestion rates and are regarded as sentinels of pollution within their foraging regions. The consumption of plastic contributes to sub-lethal impacts (i.e. morbidity, starvation) in a handful of species. Additional data on these sub-lethal effects are needed urgently to better understand the scope and severity of the plastics issue. Here we explore the application of fatty acid (FA) analysis as a novel tool to investigate sub-lethal impacts of plastic ingestion on seabird body condition and health. Using gas chromatography-mass spectrometry, we identified 37 individual FAs within the adipose, breast muscle and liver of flesh-footed (Ardenna carneipes) and short-tailed (Ardenna tenuirostris) shearwaters. We found high amounts of FA 16:0, 18:0, 20:5n3 (eicosapentaenoic acid), 22:6n3 (docosahexaenoic acid) and 18:1n9 in both species; however, the overall FA composition of the two species differed significantly. In flesh-footed shearwaters, high amounts of saturated and mono-unsaturated FAs (needed for fast and slow release energy, respectively) in the adipose and muscle tissues were related to greater bird body mass. While total FAs were not related to the amount of plastic ingested in either species, these data are a valuable contribution to the limited literature on FAs in seabirds. We encourage studies to explore other analytical tools to detect these sub-lethal impacts of plastic.

Pigment-depletion in Atlantic salmon (Salmo salar) post-smolt starved at elevated temperature is not influenced by dietary carotenoid type and increasing α-tocopherol level.

Pigment-depletion in the fillets of farmed Atlantic salmon (Salmo salar) arises after periods of elevated water temperatures with voluntary starving. This study tested the effects of dietary pre-loading with different pigment carotenoids (astaxanthin and/or canthaxanthin) combined with two α-tocopherol levels (normal and high: 500 and 1000 mg/kg, respectively) on pigment-depletion in vivo in Atlantic salmon after four weeks of challenge. We also tested whether oxidative stress manifested as an underlying depletion mechanism. Carotenoid levels in whole fillet homogenates were not decreased significantly post-challenge but fillet α-tocopherol concentrations were increased significantly in contrast to decreased oxidative stress indices. However, image analysis revealed localised fillet pigment-depletion following all dietary treatments. These data imply that localised pigment-depletion was not prevented by pre-loading of the fillet with different carotenoid-types/mixtures and increased of α-tocopherol levels from normal to high, respectively. Further, we suggest that oxidative stress might not facilitate pigment-depletion in vivo.

Meningitis and a safe dexamethasone-eluting intracochlear electrode array.

OBJECTIVES: To evaluate the potential risk of pneumococcal meningitis associated with the use of a dexamethasone-eluting intracochlear electrode array as compared with a control array. METHODS: In two phases, adult Hooded-Wistar rats were implanted via the middle ear with an intracochlear array and were inoculated with Streptococcus pneumoniae 5 days post-surgery. Phase I created a dosing curve by implanting five groups (n = 6) with a control array, then inoculating 5 days later with different numbers of S. pneumoniae: 0 CFU, 10(3) CFU, 10(4) CFU, 10(4) CFU repeated, or 10(5) CFU (colony forming units). A target infection rate of 20% was aimed for and 10(4) CFU was the closest to this target with 33% infection rate. In phase II, we implanted two groups (n = 10), one with a dexamethasone-eluting array, the other a control array, and both groups were inoculated with 10(4) CFU of S. pneumoniae 5 days post-surgery. RESULTS: The dexamethasone-eluting array group had a 40% infection rate; the control array group had a 60% infection rate. This difference was not statistically significant with a P value of ≥0.5. CONCLUSION: The use of a dexamethasone-eluting intracochlear electrode array did not increase the risk of meningitis in rats when inoculated with S. pneumoniae via the middle ear 5 days following implantation.

Contribution of a novel gene, rpeA, encoding a putative autotransporter adhesin to intestinal colonization by rabbit-specific enteropathogenic Escherichia coli.

Rabbit-specific enteropathogenic Escherichia coli (REPEC) is an attaching and effacing pathogen of young rabbits. Using signature-tagged mutagenesis, we identified several known colonization factors of REPEC as well as a gene predicted to encode a novel autotransporter protein. This novel gene was termed rpeA for REPEC plasmid-encoded autotransporter.

Contribution of long polar fimbriae to the virulence of rabbit-specific enteropathogenic Escherichia coli.

Enteropathogenic Escherichia coli (EPEC) is a major of cause of diarrhea among children in developing countries. Although EPEC is a human specific pathogen, some related strains are natural pathogens of animals, including laboratory-bred rabbits. We have identified two chromosomal loci in rabbit-specific EPEC (REPEC) O15:H- strain 83/39, which are predicted to encode long polar fimbriae (LPF). lpf(R154) was identical to a fimbrial gene cluster, lpf(O113), identified previously in enterohemorrhagic E. coli (EHEC) O113:H21. The second locus, lpf(R141), comprised a novel sequence with five predicted open reading frames, lpfA to lpfE, that encoded long fine fimbriae in nonfimbriated E. coli ORN103. The predicted products of lpf(R141) shared identity with components of the lpfABCC'DE gene cluster from EHEC O157:H7, and the fimbriae were similar in morphology and length to LPF from EHEC O157:H7. Interruption of lpf(R141) resulted in significant attenuation of REPEC 83/39 for rabbits with respect to the early stages of colonization and severity of diarrhea. However, there was no significant difference in the number of bacteria shed at later time points or in overall body weight and mortality rate of rabbits infected with lpf(R141) mutant strains or wild-type REPEC 83/39. Although rabbits infected with the lpf(R141) mutants did not develop severe diarrhea, there was evidence of attaching and effacing histopathology, which was indistinguishable in morphology, location, and extent compared to rabbits infected with wild-type REPEC 83/39. The results suggested that lpf(R141) contributes to the early stages of REPEC-mediated disease and that this is important for the development of severe diarrhea in susceptible animals.