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The differential diagnostics in Rett syndrome has evolved with the development of next generation sequencing‐based techniques and many patients have been diagnosed with other syndromes or variants in newly described genes where the associated phenotype(s) is yet to be fully explored. The term Rett‐like refers to phenotypes with distinct overlapping features of Rett syndrome where the clinical criteria are not completely fulfilled. In this study we have combined a review of Rett‐like disorders with data from a Danish cohort of 35 patients with Rett‐like phenotypes emphasizing the diagnostic overlap with Pitt‐Hopkins syndrome, Cornelia de Lange syndrome with SMC1A variants, and epileptic encephalopathies, for example, due to STXBP1 variants. We also found a patient with a pathogenic variant in KCNB1, which has not been previously linked to a Rett‐like phenotype. This study underlines the clinical and genetic heterogeneity of a Rett syndrome spectrum, and provides an overview of the Rett syndrome‐related genes described to date, and hence serves as a guide for diagnosing patients with Rett‐like phenotypes. Exploring the genes in Rett‐like phenotypes. [ABSTRACT FROM AUTHOR]

Perturbations in the gastrointestinal microbiome caused by antibiotics are a major risk factor for Clostridium difficile infection (CDI). Probiotics are often recommended to mitigate CDI symptoms; however, there exists only limited evidence showing probiotic efficacy for CDI. Here, we examined changes to the GI microbiota in a study population where probiotic treatment was associated with significantly reduced duration of CDI diarrhea. Subjects being treated with standard of care antibiotics for a primary episode of CDI were randomized to probiotic treatment or placebo for 4 weeks. Probiotic treatment consisted of a daily multi-strain capsule (Lactobacillus acidophilus NCFM, ATCC 700396; Lactobacillus paracasei Lpc-37, ATCC SD5275; Bifidobacterium lactis Bi-07, ATCC SC5220; Bifidobacterium lactis B1-04, ATCC SD5219) containing 1.7 x 1010 CFUs. Stool was collected and analyzed using 16S rRNA sequencing. Microbiome analysis revealed apparent taxonomic differences between treatments and timepoints. Subjects administered probiotics had reduced Verrucomicrobiaceae at week 8 compared to controls. Bacteroides were significantly reduced between weeks 0 to 4 in probiotic treated subjects. Ruminococcus (family Lachnospiraceae), tended to be more abundant at week 8 than week 4 within the placebo group and at week 8 than week 0 within the probiotic group. Similar to these results, previous studies have associated these taxa with probiotic use and with mitigation of CDI symptoms. Compositional prediction of microbial community function revealed that subjects in the placebo group had microbiomes enriched with the iron complex transport system, while probiotic treated subjects had microbiomes enriched with the antibiotic transport system. Results indicate that probiotic use may impact the microbiome function in the face of a CDI; yet, more sensitive methods with higher resolution are warranted to better elucidate the roles associated with these changes. Continuing studies are needed to better understand probiotic effects on microbiome structure and function and the resulting impacts on CDI. [ABSTRACT FROM AUTHOR]

Background and purpose Primary progressive apraxia of speech, a motor speech disorder of planning and programming, is a tauopathy that has overlapping histological features with progressive supranuclear palsy. We aimed to compare, for the first time, atrophy patterns, as well as white matter tract degeneration, between these two syndromes. Methods Sixteen primary progressive apraxia of speech subjects were age- and gender-matched to 16 progressive supranuclear palsy subjects and 20 controls. All subjects were prospectively recruited, underwent neurological and speech evaluations and 3.0-Tesla magnetic resonance imaging. Grey and white matter atrophy was assessed using voxel-based morphometry and atlas-based parcellation, and white matter tract degeneration was assessed using diffusion tensor imaging. Results All progressive supranuclear palsy subjects had typical oculomotor/gait impairments, but none had speech apraxia. Both syndromes showed grey matter loss in supplementary motor area, white matter loss in posterior frontal lobes and degeneration of the body of the corpus callosum. Whilst lateral grey matter loss was focal, involving superior premotor cortex, in primary progressive apraxia of speech, loss was less focal extending into prefrontal cortex in progressive supranuclear palsy. Caudate volume loss and tract degeneration of superior cerebellar peduncles were also observed in progressive supranuclear palsy. Interestingly, area of the midbrain was reduced in both syndromes compared to controls, although this was greater in progressive supranuclear palsy. Conclusions Although neuroanatomical differences were identified between these distinctive clinical syndromes, substantial overlap was also observed, including midbrain atrophy, suggesting these two syndromes may have common pathophysiological underpinnings. [ABSTRACT FROM AUTHOR]

Background The progressive supranuclear palsy syndrome ( PSPS) and corticobasal syndrome ( CBS) are associated with relatively specific patterns of atrophy; the former predominantly involving the brainstem, the latter frontoparietal regions. However, it has become apparent that there are subjects that meet criteria for PSPS and CBS. We refer to subjects with this presentation as Hybrids. The hybrid presentation is not rare, yet there are no studies that have assessed the neuroanatomical correlates of the hybrid syndrome to explain its occurrence. Method In this study of 41 subjects and controls, we utilized the technique of voxel-based morphometry to assess both gray and white matter volume loss in six prospectively recruited Hybrids that underwent 3.0 T volumetric head magnetic resonance image scanning to determine the neuroanatomical correlates of the syndrome. We compared patterns of atrophy in three prospectively recruited groups: the Hybrid group ( n = 6), a PSPS group ( n = 10), and CBS group ( n = 5). All 21 subjects had completed the same standardized batteries assessing cognition, and motor, behavioral, executive, oculomotor and limb praxis function. Results The Hybrid group showed imaging features of both PSPS and CBS, with volume loss observed in the brainstem (superior cerebellar peduncle) and cortex (medial and lateral premotor, prefrontal and motor cortex). As expected, typical patterns of loss were observed in PSPS and CBS. Conclusions These findings explain the neuroanatomical basis of the overlapping presenting signs and symptoms of PSPS and CBS, in Hybrids. [ABSTRACT FROM AUTHOR]

The ongoing rise in atmospheric pCO2 and consequent increase in ocean acidification have direct effects on marine calcifying phytoplankton, which potentially alters carbon export. To date it remains unclear, firstly, how nutrient regime, in particular by coccolithophores preferred phosphate limitation, interacts with pCO2 on particulate carbon accumulation; secondly, how direct physiological responses on the cellular level translate into total population response. In this study, cultures of Emiliania huxleyi were full-factorially exposed to two different N:P regimes and three different pCO2 levels. Cellular biovolume and PIC and POC content significantly declined in response to pCO2 in both nutrient regimes. Cellular PON content significantly increased in the Redfield treatment and decreased in the high N:P regime. Cell abundance significantly declined in the Redfield and remained constant in the high N:P regime. We hypothesise that in the high N:P regime severe phosphorous limitation could be compensated either by reduced inorganic phosphorous demand and/or by enzymatic uptake of organic phosphorous. In the Redfield regime we suggest that enzymatic phosphorous uptake to supplement enhanced phosphorous demand with pCO2 was not possible and thus cell abundance declined. These hypothesised different physiological responses of E. huxleyi among the nutrient regimes significantly altered population carrying capacities along the pCO2 gradient. This ultimately led to the attenuated total population response in POC and PIC content and biovolume to increased pCO2 in the high N:P regime. Our results point to the fact that the physiological (i.e. cellular) PIC and POC response to ocean acidification cannot be linearly extrapolated to total population response and thus carbon export. It is therefore necessary to consider both effects of nutrient limitation on cell physiology and their consequences for population size when predicting the influence of coccolithophores on atmospheric pCO2 feedback and their function in carbon export mechanisms. [ABSTRACT FROM AUTHOR]

The ongoing rise in atmospheric pCO2 and the consequent increase in ocean acidification have direct effects on marine calcifying phytoplankton which potentially translates into altered carbon export. To date it remains unclear first, how nutrient ratio, in particular from coccolithophores preferred phosphate limitation, interacts with pCO2 on particulate carbon accumulation. Second, how direct physiological responses on the cellular level translate into a net population response. In this study cultures of Emiliania huxleyi were full-factorially exposed to two different N:P ratios (Redfield and high N:P) and three different pCO2 levels. Effects on net population particulate inorganic and organic carbon (PIC, POC) were measured after E. huxleyi cultures reached stationary phase. Thereby cell sizes and total cell abundance were taken into account. Corresponding to literature results show a significant negative cellular PIC and POC response which, however, was strongest under high N:P ratio. In contrast, net population PIC and POC accumulation was significantly attenuated under high N:P ratio. We suggest that less cellular nutrient accumulation allowed for higher cell abundances which compensated for the strong negative cellular PIC and POC response to pCO2 on the population level. Moreover, the design of this study also allowed following natural alteration of carbon chemistry through changing DIC and alkalinity. Our results suggest that at high initial pCO2 natural alteration of pCO2 during the experimental runtime was regulated by algal biomass. In contrast, at low initial pCO2 the PIC/POC ratio was responsible for changes in pCO2 . Our results point to the fact that the physiological (i.e. cellular) PIC and POC response to ocean acidification cannot be linearly extrapolated to total population response and thus carbon export. It is therefore recommended to consider effects of nutrient limitation on cell physiology and translate these to net population carbon accumulation when predicting the influence of coccolithophores on both, the atmospheric pCO2 feedback and their function in carbon export mechanisms. [ABSTRACT FROM AUTHOR]

The reproductive history of 177 male patients affected with Becker (BMD) (n=69), limb-girdle (LGMD) (n=54), and facioscapulohumeral (FSHMD) (n=54) muscular dystrophy (MD) was analysed according to severity of the disease (BMD>LGMD>FSHMD) and magnitude of recurrence risk (RR) (high for FSHMD, intermediate for BMD, and low for LGMD). Additionally, 62 male patients were interviewed on psychosocial issues, in order to disentangle the factors influencing reproductive decisions among patients affected with MD. Among male adults, significantly more FSHMD than LGMD or BMD patients were married and had children. Age specific reproductive outcome was 0.31-0.32 for BMD, 0.51-0.62 for LGMD, and 0.58-1.02 for FSHMD, reflecting the influence of the disease's severity. High RRs did not significantly diminish reproduction after genetic counselling or correlate with less prospective desire for children. Instead, early onset, severity of the disease, and past reproductive history were found to diminish reproductive outcome after genetic counselling, and prospective family planning was also found to be influenced by past reproductive history as well as by emotional/sexual dysfunction with the opposite sex. [ABSTRACT FROM PUBLISHER]

A questionnaire about the interest in and demand for preclinical diagnosis for facioscapulohumeral muscular dystrophy (FSH) was sent to 46 patients. Most stated that they would have liked to have known their diagnosis earlier in order to seek more efficient help, to avoid strenuous activities, to prepare themselves emotionally, or to choose an appropriate profession. Similar arguments were used to explain their interest in preclinical diagnosis for their children. Most patients also favoured prenatal diagnosis although only two stated they would abort a pregnancy in the case of an affected fetus. Genetic counselling had apparently little influence on family planning. According to this study, FSH does not seem to reduce reproductive performance in our population. [ABSTRACT FROM PUBLISHER]

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