Effect of sodium concentration and mucosal pH on apical uptake of acetate and butyrate, and barrier function of the isolated bovine ruminal epithelium.

This study was conducted to investigate the role of Na+ on ruminal short-chain fatty acid (SCFA) absorption and barrier function when isolated ruminal epithelium was exposed to high and low pH ex vivo. Nine Holstein steer calves (322 ± 50.9 kg of body weight) consuming 7.05 ± 1.5 kg dry matter of a total mixed ration were euthanized and ruminal tissue was collected from the caudal-dorsal blind sac. Tissues were mounted between 2 halves of Ussing chambers (3.14 cm2) and exposed to buffers that contained low (10 mM) or high (140 mM) Na+ with low (6.2) or high (7.4) mucosal pH. The same buffer solutions were used on the serosal side except that pH was maintained at 7.4. Buffers used to evaluate SCFA uptake contained bicarbonate to determine total uptake or excluded bicarbonate and included nitrate to determine noninhibitable uptake. Bicarbonate-dependent uptake was calculated as the difference between the total and noninhibitable uptake. Acetate (25 mM) and butyrate (25 mM) were spiked with 2-3H-acetate and 1-14C-butyrate, respectively, and were then added to the mucosal side, incubated for 1 min, and tissues were analyzed to evaluate rates of SCFA uptake. Tissue conductance (Gt) and the mucosal-to-serosal flux of 1-3H-mannitol were used to assess barrier function. There were no Na+ × pH interactions for butyrate or acetate uptake. Decreasing mucosal pH from 7.4 to 6.2 increased total acetate and butyrate uptake, and bicarbonate-dependent acetate uptake. Flux of 1-3H-mannitol was not affected by treatment. However, high Na+ concentration reduced Gt and prevented an increase in Gt from flux period 1 to flux period 2. The results of this study indicate that although providing more Na+ to the ruminal epithelium does not affect SCFA uptake or mannitol flux, it may help stabilize tissue integrity.

[Peculiarities of preparing a patient with a cochlear implant for a magnetic resonance imaging]. / Osobennosti podgotovki patsienta s kokhlearnym implantatom k provedeniyu magnitno-rezonansnoi tomografii.

OBJECTIVE: To develop an algorithm of actions aimed at preparing a patient with a cochlear implant for magnetic resonance imaging (MRI). MATERIAL AND METHODS: A deaf patient after bilateral cochlear implantation (CI) came to St. Vladimir Children's City Clinical Hospital (Moscow) with symptoms of the demyelinating disease for MRI of the brain and spinal cord. Magnet were removed for MRI, then new magnets were installed. CONCLUSION: The temporary removing magnet for MRI of the brain and spinal cord allows to significantly reduce artifacts of MRI images.

[Formation and Unique Experience of the Center For the Treatment of Cerebrovascular Pathology in Children and Adolescents Located in a Multidisciplinary Pediatric Hospital, as the Only Primary Center of Pediatric Stroke in the Russian Federation].

Stroke is in the top ten causes of children death, ahead of brain tumors. Х-ray diagnostics development has significantly improved the detectability of pediatric stroke. The average incidence of cerebrovascular diseases in children was 13 per 100,000 children annually. The main feature of children's stroke is its multifactorial character, which complicates diagnostic process and requires involvement of doctors of different specialties to determine the leading etiological factors and choose optimal therapy and management tactics. The Center for the Treatment of Cerebrovascular Pathology in Children and Adolescents was established on the basis of Morozov Children City Clinical Hospital by Moscow Healthcare Department, Order No. 169, dated February 27, 2014. The main task was to create a pediatric stroke center on the basis of multidisciplinary Morozov Children City Clinical Hospital, which met the main international requirements of the primary center for pediatric stroke. It was done to improve early diagnostic process, refine the algorithm for maintaining patient data in acute periods, develop preventive measures, maintain city pediatric stroke register, introduce family consultations, coordinate medical care for children with cerebrovascular pathology at various levels in Moscow, and improve medical care quality for children with cerebrovascular pathology and their families. Since April 2014 more than 800 children have undergone inpatient treatment and more than 420 have been treated in outpatient departments of Morozov Children City Clinical Hospital.

The Ebola epidemic and public health response.

INTRODUCTION: An unprecedented global effort has been required to tackle the Ebola outbreak in West Africa. In this paper, we describe the contribution of Public Health England (PHE) in West Africa and the UK. SOURCES OF DATA: Public Health England AREAS OF AGREEMENT: The epidemic has been a humanitarian crisis for the three worst affected countries. PHE contributions have included expertise in outbreak control and microbiology services in West Africa, and UK preparedness for an imported case. AREAS OF CONTROVERSY: National and international systems require change to enhance the response to the next international public health crisis. GROWING POINTS: Legacy planning following the epidemic will be crucial, supporting the recovery of the health and public health systems in West Africa and ensuring that the knowledge gained during this outbreak is put to best use. AREAS TIMELY FOR DEVELOPING RESEARCH: Ongoing PHE-associated research includes efforts to understand the pathogenicity of Ebola virus disease, improve diagnostic capability, explore therapeutic options and develop new vaccines.

Primary resistance to integrase strand-transfer inhibitors in Europe.

OBJECTIVES: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance. METHODS: This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score ≥ 10 to at least one InSTI. To rule out circulation of minority InSTI-resistant HIV, 65 samples were selected for 454 integrase sequencing. RESULTS: For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIs were detected. Eleven (4%) subjects had mutations at resistance-associated positions with an HIVdb score ≥ 10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutations were detected, whereas integrase substitutions with an HIVdb score ≥ 10 were found in 8 (14.3%) individuals. CONCLUSIONS: No signature InSTI-resistant variants were circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistance were not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years.

Coherent electronic wave packet motion in C(60) controlled by the waveform and polarization of few-cycle laser fields.

Strong laser fields can be used to trigger an ultrafast molecular response that involves electronic excitation and ionization dynamics. Here, we report on the experimental control of the spatial localization of the electronic excitation in the C_{60} fullerene exerted by an intense few-cycle (4 fs) pulse at 720 nm. The control is achieved by tailoring the carrier-envelope phase and the polarization of the laser pulse. We find that the maxima and minima of the photoemission-asymmetry parameter along the laser-polarization axis are synchronized with the localization of the coherent electronic wave packet at around the time of ionization.

Health and happiness is more important than weight': a qualitative investigation of the views of parents receiving written feedback on their child's weight as part of the National Child Measurement Programme.

BACKGROUND: The present study aimed to explore parental perceptions of overweight children and associated health risks after receiving National Child Measurement Programme (NCMP) weight feedback. METHODS: Fifty-two parents of overweight and obese children aged 4-5 years and 10-11 years enrolled in the NCMP programme in England in 2010-2011 participated in qualitative, semi-structured interviews about their perceptions of their child's weight and health risk after receiving weight feedback. Interviews were audio tape recorded and were conducted either by telephone (n = 9) or in the respondents' homes (n = 41). Interviews were transcribed verbatim and analysed using interpretative thematic analysis. RESULTS: Parents who received NCMP written feedback informing them that their child was overweight disregarded the results because they viewed 'health and happiness as being more important than weight'. The feedback was viewed as less credible because it did not consider the individual child's lifestyle.'Broad definitions of healthy' were described that did not include weight,such as reference to the child having good emotional and physical health and a healthy diet. Parents attributed weight to 'inherited/acquired factors' such as genetics or puppy fat, or did not regard their child's 'appearance' as reflecting being overweight. 'Cultural influence' also meant that being overweight was not viewed negatively by some non-white parents. CONCLUSIONS: After receiving written weight feedback, parents use methods other than actual weight when evaluating their child's weight status and health risks. Parents' conceptions of health and weight should be considered when communicating with parents, with the aim of bridging the gap between parental recognition of being overweight and subsequent behaviour change.

Differences in intestinal mucin dynamics between germ-free and conventionally reared chickens after mannan-oligosaccharide supplementation.

A germ-free (GF) chicken model was used to test 2 hypotheses: 1. microbial colonization of the gastrointestinal tract (GIT) influences mucin gene expression and mucin types; and 2. mannan oligosaccharide (MOS) supplementation affects GIT cells directly, without bacteria mediation, compared with bacterial-mediated effect (i.e., indirectly). Gnotobiotic isolators were used: 1) GF, 2) with a single bacteria population, and 3) conventionalized by exposure to cecal bacterial contents. Each was divided to 2 diet groups: with or without MOS (2 kg/t) for 1 wk. Results show that the absence of bacteria in the GIT caused a reduction in neutral and acidic goblet cell (GC) number and density, an increase in sulfated mucin, absence of sialylated GC, and reduced mucin 2 mRNA expression in the small intestine of GF compared with conventional birds. These results indicate a reduced development of mucin production and secretion in the absence of GIT bacteria implying a less mature small intestine mucosa, supporting our first hypothesis. Results from the single bacteria population group were not conclusive and did not support any of the hypotheses. Supplementation of MOS, regardless of microbial presence, caused a reduction in neutral GC number and density but increased neutral GC area. The MOS caused different effects on acidic mucins in conventional and GF birds, causing a reduction in sialylated GC number (conventional) and a reduction in sulfated GC density (GF), all supporting a direct effect of MOS in GF animals, in addition to an indirect effect via gut microflora.

Toll-like receptor-4 expression in infants with pertussis infection.

PURPOSE: Our aim was to evaluate the expression of Toll-like receptor-4 (TLR-4) and the level of interferon-gamma (IFN-γ) and interleukin-10 (IL-10) in young infants infected by Bordetella pertussis and B. parapertussis. METHODS: Twenty-two infants under the age of 3.5 months with the clinical suspicion of pertussis were enrolled in the study. Nasopharyngeal secretions were obtained for laboratory testing, and blood samples were obtained for flow cytometry and cytokine level analysis. RESULTS: Six infants had positive PCR results for pertussis; the other 16 infants had infections attributable to another causal agent and were used as the control group. The mean fluorescence index, used as a measure of TLR-4 expression by monocytes, was significantly lower in infants with pertussis than in the control group infants (34.32 ± 18.58 vs. 63.14 ± 28, respectively; p = 0.041). The serum IFN-γ level was also significantly lower in infants with pertussis than in the control group patients (0.41 ± 0.58 vs. 1.36 ± 1.87, respectively; p = 0.04). No differences were found in the levels of IL-10. CONCLUSIONS: Based on these results, we suggest that TL4 expression by monocytes and serum INF-γ levels are lower in infants with positive PCR results for pertussis than in infants with a non-pertussis upper respiratory tract infection.

Effect of day length on cause of mortality, leg health, and ocular health in broilers.

An experiment was conducted to study the effect of day length, sex, and genotype (Ross × Ross 308 and 708) on mortality causes, bird mobility, footpad health, and ocular size, with 4 trials within the experiment. Four graded day lengths were chosen to allow the study of relationship between day length and health parameters, including 14L:10D, 17L:7D, 20L:4D, and 23L:1D. The primary statistical tools used to assess the day length relationships were regression analysis (Proc Reg and RSReg of SAS). Data were also analyzed as a 4 (lighting program) × 2 (sex) × 2 (genotype) factorial arrangement. Total mortality, as well as mortality due to metabolic and skeletal disease, decreased linearly with increasing inclusion of darkness (7- to 32-, 7- to 38-, and 7- to 48-d periods). Infectious disorders were quadratically related to day length (7- to 48-d period only), with birds under 20L having the highest level. Day length was linearly or quadratically related to average gait score in a positive fashion, and the incidence of birds falling in painful gait score categories increased linearly with increasing day length. Average footpad lesion scores increased with increasing day length (28 and 35 d). The 23L photoperiod resulted in heavier eye weights than other lighting programs. Males had a higher mortality and morbidity rate and a higher average gait score than females. Average footpad score was lower for males than females (28 and 35 d). Overall mortality was higher for 308 than 708 broilers; hence, levels of specific mortality causes were higher. Average gait scores were lower for 308 than 708 birds in 2 of the 3 time periods measured and footpad lesions were higher. To conclude, many aspects of broiler health improve with decreasing day length.

[Stroke in children: experience of the Center for the Treatment of Cerebrovascular Diseases in Children and Adolescents in Moscow]. / Insul't u detei: opyt raboty Tsentra po lecheniyu tserebrovaskulyarnykh zabolevanii u detei i podrostkov Moskvy.

OBJECTIVE: To analyze the work of the Center for the Treatment of Cerebrovascular Pathology in Children and Adolescents, operating on the basis of the Morozov Children's City Clinical Hospital of the Moscow Health Department for the period 2018-2021 and to assess the peculiarities of organizing the provision of specialized care to children and adolescents with acute cerebrovascular accident (ACA). MATERIAL AND METHODS: Annual reports of the Center for the period 2018-2021; included children and adolescents aged 1 month to 17 years 11 months 29 days, with new onset ischemic stroke (IS) and hemorrhagic stroke (HS), cerebral venous thrombosis (sinus thrombosis), confirmed clinically and radiologically. RESULTS: Statistical data on stroke and organization of care for children with this pathology in Moscow are presented. The incidence of IS in Moscow for the period 2018-2021 ranged from 1.6 to 2.5 per 100.000 children, HI - from 2.35 to 3.3 per 100.000, sinus thrombosis from 0.5 to 1.38 per 100.000. When assessing the main etiological factors of stroke in The Center for International Pediatric Stroke Research categories, we noted a prevalence of chronic head and neck diseases (20-37%) and chronic systemic conditions (conditions or diseases with known changes in coagulation or vascular structure, including connective tissue dysplasia, genetic, hematological, inflammatory or diseases of the immune system) (15-20%). In addition, data on reperfusion therapy carried out at the Center are presented. From 2018 (first thrombolysis was performed) to 2021, 7.3-14.7% of all patients with IS underwent thrombolysis. CONCLUSION: The experience of functioning of the Center for the Treatment of Cerebrovascular Pathology in Children and Adolescents has shown that the creation of such centers in the regions of the Russian Federation is relevant, but requires taking into account the characteristics of the pediatric population when organizing their work.

The autoreactivity of B cells in hereditary angioedema due to C1 inhibitor deficiency.

Patients with hereditary angioedema (HAE) tend to produce autoantibodies and have a propensity to develop immunoregulatory disorders. We characterize the profile of autoantibodies in a group of HAE patients and investigate their memory B cells' phenotype and activation status. We studied the activity status phenotype, Toll-like receptor (TLR)-9 expression and total phosphotyrosine in B cells isolated from HAE patients. Additionally, the following autoantibodies were assessed in the serum of 61 HAE patients: anti-nuclear, rheumatoid factor, anti-cardiolipin, anti-tissue transglutaminase, anti-endomysial, anti-Saccharomyces cerevisiae, anti-thyroid and anti-neutrophil cytoplasmic antibodies. In 47·5% of HAE patients we detected at least one of the tested autoantibodies. Expression of CD69, CD5 and CD21 was found to be significantly higher on memory B cells from HAE patients compared to healthy controls (4·59 ± 4·41 versus 2·06 ± 1·81, P = 0·04, 8·22 ± 7·17 versus 3·65 ± 3·78, P = 0·05, 2·43 ± 0·54 versus 1·92 ± 0·41, P = 0·01, respectively). Total phosphotyrosine in B cells from HAE patients was significantly higher compared to healthy controls (4·8 ± 1·1 versus 2·7 ± 1·3, P = 0·0003). Memory B cells isolated from the HAE group contained higher amounts of TLR-9 compared to healthy controls (8·17 ± 4·1 versus 4·56 ± 1·6, P = 0·0027). Furthermore, the expression of TLR-9 in memory B cells from HAE patients with autoantibodies was significantly higher than the control group (10 ± 4·7 versus 4·56 ± 1·6, P = 0·0002) and from that in HAE patients without autoantibodies (10 ± 4·7 versus 5·8 ± 0·9, P = 0·036). HAE patients have enhanced production of autoantibodies due most probably to the increased activation of B cells, which was found to be in association with a high expression of TLR-9.

B cell-activating factor enhances interleukin-6 and interleukin-10 production by ODN-activated human B cells.

We aim to investigate the additive value of B cell-activating factor (BAFF) when added to oligodeoxynucleotides (ODN)-activated B cells with respect to TLR-9, CD69, MHC-II expression, IL-6 and IL-10 secretion and B cell cycling. Therefore, B cells from healthy individuals were incubated under the following conditions: (1) B cells with medium, (2) B cells with ODN 0.5 µm, (3) B cells with BAFF 20 µm and (4) B cells with both ODN 0.5 µm and BAFF 20 µm. We found that addition of BAFF did not enhance the expression of TLR-9, CD69 and MHC-II in ODN-activated B cells. Incubation of B cells with BAFF and ODN together leads to a marked elevation of IL-6 and IL-10 levels compared to ODN alone. Synthesis and mitosis were higher in B cells stimulated by BAFF than in B cells stimulated by ODN. These findings suggest that both BAFF and TLR-9 contribute independently to B cell function.

Dose-dependent effects of dietary zinc oxide on bacterial communities and metabolic profiles in the ileum of weaned pigs.

Pharmacological levels of zinc oxide (ZnO) can improve the health of weaning piglets and influence the intestinal microbiota. This experiment aimed at studying the dose-response effect of five dietary concentrations of ZnO on small intestinal bacteria and metabolite profiles. Fifteen piglets, weaned at 25 ± 1 days of age, were allocated into five groups according to body weight and litter. Diets were formulated to contain 50 (basal diet), 150, 250, 1000 and 2500 mg zinc/kg by adding analytical-grade (>98% purity) ZnO to the basal diet and fed ad libitum for 14 days after a 7-day adaptation period on the basal diet. Ileal bacterial community profiles were analysed by denaturing gradient gel electrophoresis and selected bacterial groups quantified by real-time PCR. Concentrations of ileal volatile fatty acids (VFA), D- and L-lactate and ammonia were determined. Species richness, Shannon diversity and evenness were significantly higher at high ZnO levels. Quantitative PCR revealed lowest total bacterial counts in the 50 mg/kg group. Increasing ZnO levels led to an increase (p = 0.017) in enterobacteria from log 4.0 cfu/g digesta (50 mg/kg) to log 6.7 cfu/g digesta (2500 mg/kg). Lactic acid bacteria were not influenced (p = 0.687) and clostridial cluster XIVa declined (p = 0.035) at highest ZnO level. Concentration of total, D- and L-lactate and propionate was not affected (p = 0.736, p = 0.290 and p = 0.630), but concentrations of ileal total VFA, acetate and butyrate increased markedly from 50 to 150 mg/kg and decreased with further increasing zinc levels and reached low levels again at 2500 mg/kg (p = 0.048, p = 0.048 and p = 0.097). Ammonia decreased (p < 0.006) with increasing dietary ZnO level. In conclusion, increasing levels of dietary ZnO had strong and dose-dependent effects on ileal bacterial community composition and activity, suggesting taxonomic variation in metabolic response to ZnO.

Functional amino acid supplementation postweaning mitigates the response of normal birth weight more than for low birth weight pigs to a subsequent Salmonella challenge.

Previous work has shown that dietary supplementation with key functional amino acids (FAA) improves growth performance and immune status of disease-challenged normal birth weight (NBW) pigs. It is not known whether FAA supplementation attenuates the effects of a subsequent disease challenge or whether this response is similar in low birth weight (LBW) pigs. The objective was to determine the effects of birth weight and FAA supplementation during the postweaning period in Salmonella-challenged pigs. Thirty-two LBW (1.08 ± 0.11 kg) and NBW (1.58 ± 0.11 kg) pigs were assigned to a nursery feeding program at weaning (25 d) for 31 days in a 2 × 2 factorial arrangement. Factors were birth weight category (LBW vs. NBW) and basal (FAA-) or supplemented FAA profile (FAA+; Thr, Met, and Trp at 120% of requirements). At d 31, pigs were placed onto a common grower diet and, after a 7-d adaptation period, were inoculated with Salmonella Typhimurium (ST; 2.2 × 109 colony-forming units/mL) and monitored for 7-d postinoculation. Growth performance, rectal temperature, fecal score, indicators of gut health, ST shedding score in feces, intestinal ST colonization and translocation, and blood parameters of acute-phase response and antioxidant balance were measured pre- and postinoculation. Inoculation with ST increased temperature and fecal score, and the overall rectal temperature was higher in LBW compared to NBW pigs (P < 0.05). Postinoculation (d 7), reduced:oxidized glutathione was increased in NBW compared to LBW pigs (P < 0.05). Salmonella shedding and translocation to spleen were lower in NBW-FAA+ compared to NBW-FAA- pigs (P < 0.05). Postinoculation average daily gain was higher in NBW-FAA+ (P < 0.05) compared to the other groups. Postinoculation haptoglobin, superoxide dismutase, and colonic myeloperoxidase were increased in LBW-FAA- pigs (P < 0.05). Ileal alkaline phosphatase was decreased in LBW compared to NBW (P < 0.05). Overall, FAA supplementation represents a potential strategy to mitigate the effect of enteric disease challenge in NBW, but not LBW pigs.

[Stroke in children and adolescents]. / Insul't u detei i podrostkov.

OBJECTIVE: A comparative analysis of symptoms in arterial ischemic and stroke-like conditions in children, the development and analysis of the «Presumptive stroke in children¼ scale for prehospital diagnosis of ischemic strokes in children. MATERIAL AND METHODS: This article analyzes cases of emergency hospitalization of children in a stroke center with suspected cerebrovascular pathology as well as the symptoms of patients with suspected ischemic stroke, compares the leading and final diagnoses, identifies the main «mimics¼ of stroke and their symptom complexes. A comparison of the obtained data with the results of previous studies was carried out. RESULTS: The results show the prevalence of motor disorders and coordination disorders in cases of ischemic stroke and cerebral symptoms in cases of stroke-like conditions in children. The most frequent stroke-mimic is migraine. Based on the results of the study, we propose a screening scale for pre-hospital diagnosis of ischemic stroke in children. A preliminary assessment of the effectiveness of the scale using examples of cases of confirmed stroke and stroke-mimic was performed. CONCLUSION: Timely hospitalization of children with stroke can not only reduce mortality, but also use modern diagnostic and treatment methods to reduce the volume of brain damage with a possible complete restoration of motor and cognitive functions. Further analysis of the sensitivity and specificity of the «Presumptive stroke in children¼ scale is required.

SNP array analysis in constitutional and cancer genome diagnostics--copy number variants, genotyping and quality control.

Array-based comparative genomic hybridization analysis of genomic DNA was first applied in postnatal diagnosis for patients with intellectual disability (ID) and/or congenital anomalies (CA). Genome-wide single-nucleotide polymorphism (SNP) array analysis was subsequently implemented as the first line diagnostic test for ID/CA patients in our laboratory in 2009, because its diagnostic yield is significantly higher than that of routine cytogenetic analysis. In addition to the detection of copy number variations, the genotype information obtained with SNP array analysis enables the detection of stretches of homozygosity and thereby the possible identification of recessive disease genes, mosaic aneuploidy, or uniparental disomy. Patient-parent (trio) information analysis is used to screen for the presence of any form of uniparental disomy in the patient and can determine the parental origin of a de novo copy number variation. Moreover, the outcome of a genotype analysis is used as a final quality control by ruling out potential sample mismatches due to non-paternity or sample mix-up. SNP array analysis is now also used in our laboratory for patients with disorders for which locus heterogeneity is known (homozygosity pre-screening), in prenatal diagnosis in case of structural ultrasound anomalies, and for patients with leukemia. In this report, we summarize our array findings and experiences in the various diagnostic applications and demonstrate the power of a SNP-based array platform for molecular karyotyping, because it not only significantly improves the diagnostic yield in both constitutional and cancer genome diagnostics, but it also enhances the quality of the diagnostic laboratory workflow.

Intra-individual stability over time of standardized anti-Mullerian hormone in FMR1 premutation carriers.

BACKGROUND: Carriers of a premutation (CGG repeat length 55-200) in the fragile X mental retardation (FMR1) gene are at risk for primary ovarian insufficiency (FXPOI). The anti-Müllerian hormone (AMH) level acts as a useful marker of ovarian follicle reserve and, thus, may serve to predict when this ovarian reserve becomes too low to sustain ovarian function. We investigated the intra-individual variation of AMH levels over time for premutation carriers compared with non-carriers. METHODS: We determined AMH levels in blood samples from 240 women ascertained through fragile X families, of which 127 were premutation carriers and 113 were non-carriers. Linear mixed models were used to assess the effect of age and premutation status on AMH levels and to determine a modeled AMH value. The stability over time of the deviation of observed AMH levels from modeled levels, referred to as standardized AMH values, was assessed through correlation coefficients of 41 longitudinal samples. RESULTS: At all ages, premutation carriers exhibited lower AMH levels. For all women, AMH was found to decrease by 10% per year. The added effect of having a premutation decreased AMH levels by 54%. The deviation of an individual's AMH level from the modeled value showed a reasonable intra-individual correlation. The Pearson correlation coefficient of two samples taken at different ages was 0.36 (P = 0.05) for non-carriers and 0.69 (P = 0.01) for carriers. CONCLUSIONS: We developed a unique standardized AMH value, taking FMR1 premutation status and the subject's age into account, which appears to be stable over time and may serve as a predictor for FXPOI after further longitudinal assessment.