Evolution of clinical and radiological presentations of spondyloepimetaphyseal dysplasia, RPL13-related: Description of 11 further cases.

Spondyloepimetaphyseal dysplasia (SEMD), RPL13-related is caused by heterozygous variants in RPL13, which encodes the ribosomal protein eL13, a component of the 60S human ribosomal subunit. Here, we describe the clinical and radiological evolution of 11 individuals, 7 children and 4 adults, from 6 families. Some of the skeletal features improved during the course of this condition, whilst others worsened. We describe for the first time "corner fractures" as a feature of this dysplasia which as with other dysplasias disappear with age. In addition, we review the heights and skeletal anomalies of these reported here and previously in a total of 25 individuals from 15 families. In this study, six different RPL13 variants were identified, five of which were novel. All were located in the apparently hotspot region, located in intron 5 and exon 6. Splicing assays were performed for two of the three previously undescribed splicing variants. Until now, all splice variants have occurred in the intron 5 splice donor site, incorporating an additional 18 amino acids to the mutant protein. Here, we report the first variant in intron 5 splice acceptor site which generates two aberrant transcripts, deleting the first three and four amino acids encoded by exon 6. Thus, this study doubles the number of SEMD-RPL13-related cases and variants reported to date and describes unreported age-related clinical and radiological features.

TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.

Dysfunction of the gonadotropin-releasing hormone (GnRH) axis causes a range of reproductive phenotypes resulting from defects in the specification, migration and/or function of GnRH neurons. To identify additional molecular components of this system, we initiated a systematic genetic interrogation of families with isolated GnRH deficiency (IGD). Here, we report 13 families (12 autosomal dominant and one autosomal recessive) with an anosmic form of IGD (Kallmann syndrome) with loss-of-function mutations in TCF12, a locus also known to cause syndromic and non-syndromic craniosynostosis. We show that loss of tcf12 in zebrafish larvae perturbs GnRH neuronal patterning with concomitant attenuation of the orthologous expression of tcf3a/b, encoding a binding partner of TCF12, and stub1, a gene that is both mutated in other syndromic forms of IGD and maps to a TCF12 affinity network. Finally, we report that restored STUB1 mRNA rescues loss of tcf12 in vivo. Our data extend the mutational landscape of IGD, highlight the genetic links between craniofacial patterning and GnRH dysfunction and begin to assemble the functional network that regulates the development of the GnRH axis.

Effect of a Prebiotic Formulation on Frailty Syndrome: A Randomized, Double-Blind Clinical Trial.

Aging can result in major changes in the composition and metabolic activities of bacterial populations in the gastrointestinal system and result in impaired function of the immune system. We assessed the efficacy of prebiotic Darmocare Pre(®) (Bonusan Besloten Vennootschap (BV), Numansdorp, The Netherlands) to evaluate whether the regular intake of this product can improve frailty criteria, functional status and response of the immune system in elderly people affected by the frailty syndrome. The study was a placebo-controlled, randomized, double blind design in sixty older participants aged 65 and over. The prebiotic product was composed of a mixture of inulin plus fructooligosaccharides and was compared with placebo (maltodextrin). Participants were randomized to a parallel group intervention of 13 weeks' duration with a daily intake of Darmocare Pre(®) or placebo. Either prebiotic or placebo were administered after breakfast (between 9-10 a.m.) dissolved in a glass of water carefully stirred just before drinking. The primary outcome was to study the effect on frailty syndrome. The secondary outcomes were effect on functional and cognitive behavior and sleep quality. Moreover, we evaluated whether prebiotic administration alters blood parameters (haemogram and biochemical analysis). The overall rate of frailty was not significantly modified by Darmocare Pre(®) administration. Nevertheless, prebiotic administration compared with placebo significantly improved two frailty criteria, e.g., exhaustion and handgrip strength (p < 0.01 and p < 0.05, respectively). No significant effects were observed in functional and cognitive behavior or sleep quality. The use of novel therapeutic approaches influencing the gut microbiota-muscle-brain axis could be considered for treatment of the frailty syndrome.

Serum vitamin D and functional impairment in octogenarian women.

PURPOSE: Serum vitamin D deficiency has been associated with frailty in people aged 65 and over, however its relationship with functional impairment has not been investigated in octogenerian (aged 80-90 years) institutionalized women. METHODS: We assessed functional impairment in this latter group by measuring frailty syndrome and other geriatric and psychological assessment scales: the Tinetti gait and balance index to determine the risk for falls, the Barthel index to measure the basic activities of daily living, the Lawton index for instrumental activities, the mini-mental score examination test for cognitive impairment, the Yesavage scale for geriatric depression, and the Norton scale for the risk of ulceration. RESULTS: Frail individuals had significantly reduced serum vitamin D concentrations (measured as total 25-hydroxyvitamin D; 25(OH)D) compared to robust individuals, but reduced 25(OH)D concentration did not significantly correlate with frailty syndrome severity, and mean 25(OH)D concentrations were within the recommended levels in all groups. The 25(OH)D concentration did not correlate with any of the blood analytical parameters measured and with the geriatric assessment scales used, suggesting a selective relationship with frailty. CONCLUSION: These results highlight the need to individualize treatment such as vitamin D supplementation in order to treat frailty syndrome.

Relationship between mobility and cognitive impairment in patients with Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is usually accompanied by impairments to mobility, performance of the basic activities of daily life (ADL), and progressive cognitive decline. We analyzed the relationship between cognitive performance and related cognitive subdomains and mobility. PATIENTS AND METHODS: All AD patients of the recruited individuals were living in nursing homes; they underwent a blood analysis, cognitive examination by using the Mini-Mental State Examination, functional evaluation of independence in the ADLs with Barthel score and Katz index, and mobility assessment with the elderly mobility scale. RESULTS: The mean sample age was 84 years and majority were women; more than 60% of the participants had severe cognitive impairment. Statistically significant relationships were found between the severity of cognitive impairment and functional capacity (p < 0.01) and their degree of mobility (p < 0.05). Among the different domains, memory impairment was not associated with impaired mobility or ability to perform the ADLs. Women had lower scores in the ADL and mobility assessments (p < 0.05) and an increased ratio of severe cognitive impairment (OR = 3.03 95% CI: [1.30, -7.05]) compared to men. Being overweight or obese and high blood levels of HDL cholesterol were directly (p < 0.05) and inversely (p < 0.01) associated with poor cognitive performance in individuals with mild to moderate cognitive dysfunction, respectively. CONCLUSIONS: This study shows that better functional capacity and mobility are generally, but not exclusively, correlated with better cognitive function, depending on the severity of cognitive impairment. In contrast, lipid profile alterations might play a role in cognitive deficits in individuals with mild to moderate cognitive impairment who are overweight. Further longitudinal studies will be required to explore this possibility.

Protein features for assembly of the RNA editing helicase 2 subcomplex (REH2C) in Trypanosome holo-editosomes.

Uridylate insertion/deletion RNA editing in Trypanosoma brucei is a complex system that is not found in humans, so there is interest in targeting this system for drug development. This system uses hundreds of small non-coding guide RNAs (gRNAs) to modify the mitochondrial mRNA transcriptome. This process occurs in holo-editosomes that assemble several macromolecular trans factors around mRNA including the RNA-free RNA editing core complex (RECC) and auxiliary ribonucleoprotein (RNP) complexes. Yet, the regulatory mechanisms of editing remain obscure. The enzymatic accessory RNP complex, termed the REH2C, includes mRNA substrates and products, the multi-domain 240 kDa RNA Editing Helicase 2 (REH2) and an intriguing 8-zinc finger protein termed REH2-Associated Factor 1 (H2F1). Both of these proteins are essential in editing. REH2 is a member of the DExH/RHA subfamily of RNA helicases with a conserved C-terminus that includes a regulatory OB-fold domain. In trypanosomes, H2F1 recruits REH2 to the editing apparatus, and H2F1 downregulation causes REH2 fragmentation. Our systematic mutagenesis dissected determinants in REH2 and H2F1 for the assembly of REH2C, the stability of REH2, and the RNA-mediated association of REH2C with other editing trans factors. We identified functional OB-fold amino acids in eukaryotic DExH/RHA helicases that are conserved in REH2 and that impact the assembly and interactions of REH2C. H2F1 upregulation stabilized REH2 in vivo. Mutation of the core cysteines or basic amino acids in individual zinc fingers affected the stabilizing property of H2F1 but not its interactions with other examined editing components. This result suggests that most, if not all, fingers may contribute to REH2 stabilization. Finally, a recombinant REH2 (240 kDa) established that the full-length protein is a bona fide RNA helicase with ATP-dependent unwinding activity. REH2 is the only DExH/RHA-type helicase in kinetoplastid holo-editosomes.

Low docosahexaenoic acid in the diet and milk of women in New Mexico.

Because docosahexaenoic acid (DHA) is critical for the development of the nervous system, especially during the first year of life, the content of DHA in human milk is important for the well-being of exclusively breastfed infants. The aim of this study was to determine the fatty acid composition, including DHA, of the breast milk fat and serum phospholipids of women in New Mexico, and to correlate these data with dietary fatty acid content. Samples of blood and breast milk, 3-day diet records, and information on dietary supplement use were obtained from 29 women. Eligible subjects were nonsmokers, aged 18 to 40 years, lactating for 1 to 6 months, and not pregnant, taking immunosuppressive drugs, or diagnosed with diabetes. The mean fat content of the breast milk was 3.37+/-2.34 g/dL. The percentage of DHA in the milk fat was very low (0.11%) relative to international norms (0.2% to 0.4%) and could be explained by the women's low intake of DHA (33 to 58 mg/day). These data can be explained by the fact that the subjects were not taking DHA supplements or consuming foods that are good sources of DHA. Correlations were found between the percentages of DHA in the serum phospholipids and milk fat. The findings underscore the need for educating lactating women about food sources of DHA. Educational opportunities could occur in conjunction with other education postdelivery or during postnatal clinic visits.

Subjective and objective sleep quality in elderly individuals: The role of psychogeriatric evaluation.

Aging affects sleep and sleep problems are common in older individuals. However, the relationship between objective and subjective tools for analysing sleep and psycho-geriatric variables have not been tested in institutionalised older individuals. This work analyses sleep quality by using actigraphy as an objective tool and validates the Athens and Oviedo sleep questionnaires in octogenarian elderly individuals as subjective scales of sleep perception. All patients wore an actigraph device for one week and then completed the Athens and Oviedo clinical sleep-evaluation questionnaires. Morning cortisol levels in blood plasma and saliva samples were also measured to assess the association between objective and reported sleep patterns. Age, gender, and psycho-geriatric evaluations, including Barthel, Tinetti, and Mini-Mental scale measurements were analysed as variables with the potential to confound the strength of any such associations. There was a significant inverse correlation between the number of awakenings and the time spent awake during night assessed by actigraphy and the total Oviedo questionnaire score, but no significant associations for the other parameters. The blood cortisol concentration appears to be a marker of insomnia related to sleep times of less than four hours and diagnosis of insomnia based on Athens scale and thus, represents a potential marker for sleep interventions.

Frailty and leucocyte count are predictors of all-cause mortality and hospitalization length in non-demented institutionalized older women.

Alteration in the immune system such as the number of white blood cells count (WBC) has been associated with frailty syndrome but their role in institutionalized older individuals have been rarely investigated. We evaluated the relationships between white blood cell subtypes, geriatric assessment, depression and frailty syndrome based on the criteria of physical phenotype. In particular, we aimed to analyze by a two-year follow-up and prospective study the predictive value of alterations in WBC, frailty and functional impairment in terms of hospitalizations and all-cause mortality in institutionalized older women. There was a significant and inverse correlation between the frailty score and lymphocyte count at baseline but it did not display any predictive effect for the outcomes (hospitalizations and mortality). In contrast, monocytes count was significantly correlated with number of hospital stays and predicted hospitalizations in the follow-up. High frailty score directly and better functional status (Barthel score) inversely predicted mortality in the follow-up with an HR of 1.87 (95%CI: 1.04-3.35), and 0.97 (95% CI: 0.96-0.99) (p < .05 in both cases). Further investigation into the role of white blood cell subtypes in aging and its associated adverse outcomes in older adults is warranted. Physical phenotype of frailty besides general population, also predicted mortality in older institutionalized women and deserves specific intervention in this subgroup of older individuals.

[Effects of a physical restraint removal program on older people with dementia in residential care]. / Efectos de un programa de eliminación de sujeciones físicas sobre personas mayores con demencia en residencias.

OBJECTIVE: To analyse the results of removing physical restraints from elderly patients with dementia living in nursing homes. This objective is part of a wider process of change in residential care. METHODS: Quasi-experimental study conducted in two residences from May 2010 to May 2012. Information was collected at 7 time points and longitudinal analyses were performed. After training staff, the physical restraints in El Puig centre were phased out, while in the Conarda centre, restraints were still applied to elderly people. The main variables studied were: falls, psychotropic medication prescriptions, different indicators of mental impairment, and degree of dependence (Norton, NPI, Mini-mental, Tinetti, Barthel). RESULTS: In the El Puig centre all the physical restraints were removed. A slight improvement was seen in the number of falls, and their consequences. The ANOVA showed significant improvements in the centre that removed restraints in prescribing psychotropic medications, cognitive impairment, and behavioural changes. DISCUSSION: It is shown that removing physical restraints do not cause negative effects as regards the number of falls, and also positively affects the welfare and independence of elderly people (through changes in behaviour and mental impairment). Furthermore, it is demonstrated that this program must be accompanied by the reduction and control of medicines (withdrawal of the number of psychotropic prescriptions).

Sleep Alterations in Non-demented Older Individuals: The Role of Cortisol.

BACKGROUND: Sleep alterations can impair quality of life and contribute to disease progression but they, and their features and contributing factors, are rarely analysed in institutionalised older individuals. In this study, we investigated sleep alterations, the factors involved, and the role of cortisol in sleep-related problems in institutionalised individuals. METHODS: We conducted a descriptive cross-sectional study in participants living in nursing homes in Valencia (Spain); sleep alterations were determined based on two validated tools: the Athens insomnia scale and Oviedo sleep questionnaire. Plasma cortisol was measured in the morning and determined by high performance liquid chromatography-mass spectroscopy, along with other blood analytical parameters. We also analysed any confounding factors (sleep duration, morning awakening time, intake of hypnotic and psychotropic medication, and cognitive function). RESULTS: The mean age was 82.5 years (range: 65-99); approximately 80% were women and sleep alterations were present in 25-60% of the population, depending on the scale used or type of sleep disorder considered. There was no significant correlation between morning cortisol concentrations and sleep disorders, sex, age, or psychotropic drug ingestion (including hypnotic drugs). However, there was a significant correlation between cortisol and an Oviedo questionnaire subscale for evaluating insomniarelated adverse events, which remained significant after adjusting for multiple potentially confounding factors. CONCLUSION: Sleep disorders are common in institutionalised older individuals and are not related to sleep duration or decreased by ingestion of hypnotic medications. There is a significant relationship between morning cortisol levels in blood and insomnia-related sleep disorders (e.g. snoring with awakenings, nightmares, restless legs syndrome, etc.) but not directly with insomnia or hypersomnia.

Brain-derived neurotrophic factor correlates with functional and cognitive impairment in non-disabled older individuals.

We used a complete battery of geriatric and psychometric tests to evaluate whether plasma-borne brain-derived neurotrophic factor (BDNF), a master molecule in neuroplasticity, is associated with the severity of functional and cognitive impairment in non-disabled older individuals. There was a significant positive correlation between BDNF plasma concentrations and the Barthel index, a measurement of the ability of individuals to perform the activities of daily living (p=0.03) and the concentration subcategory measured with the mini mental state examination (MMSE) test (p = 0.01). Furthermore, plasma BDNF inversely and significantly correlated with the blood eosinophil count (p = 0.01), the total cholesterol concentration (p = 0.04), and high-density lipoprotein cholesterol (p=0.04). However, BDNF did not correlate with any other socio-demographic or clinical characteristics, other analytical parameters measured in the blood, or any other geriatric assessment scales. Our results suggest that BDNF may play a role in the pathophysiology of functional impairment in the elderly and in some aspects of cognitive function. However, more studies are needed to understand the relationship between circulating BDNF and functional impairment to determine if BDNF represents a candidate biomarker for this type of cognitive impairment.

Triple-negative breast cancer: what is known about it?

Triple-negative breast cancer (TNBC) is considered a rare diagnosis. This malignancy targets a specific population of women and has risk factors differing from those of other breast cancers. TNBC exhibits distinct pathologic features that result in aggressive metastasis and poor prognosis. Pathologically, TNBC cancer cells are characterized by negative receptors for progesterone and estrogen and by the lack of over-expression of human epidermal growth factor receptor 2, which limits chemotherapeutic treatment options for women with TNBC. Nurses can assist in early detection by offering patient education about the little known risk factors for TNBC. Psychosocial issues can overwhelm patients diagnosed with breast cancer. This article provides suggestions for nurses as they guide women who are experiencing an atypical breast cancer diagnosis with an uncertain prognosis and limited treatment options.

The value of neutrophil and lymphocyte count in frail older women.

Increasing evidence suggests that systemic inflammation is associated with many pathophysiological processes including frailty in older adults. We evaluated the relationships between white blood cell subtypes, geriatric assessment, and frailty syndrome and in particular, how they correlate with individual frailty criteria (involuntary loss of weight, low energy or exhaustion, slow mobility, muscle weakness, and low physical activity) in frail older women. There was a significant and positive correlation between the frailty score and neutrophil count, but a significantly negative correlation was found when this score was compared to the lymphocyte count. These associations were significant only for two frailty criteria: poor muscular strength and low physical activity. Further investigation into the role of white blood cell subtypes in ageing and its associated adverse outcomes in older adults is warranted, in particular in the loss of muscular strength and for poor physical activity.

Intestinal obstruction due to foreign body in a patient with adenocarcinoma of the colon: case report.

BACKGROUND: Approximately one million new cases of colorectal cancer are detected worldwide, causing about one million deaths per year. In Mexico it is the second most common gastrointestinal malignancy, after stomach cancer. The 5-year survival in early stages is > 90%. This condition is incidentally diagnosed by the general surgeon in many cases because ingestion of foreign bodies is a not uncommon condition in adults, reported more frequently in older people because of their dentures. One complication of ingestion of any foreign body is intestinal obstruction. The aim of this study is to analyze management of colon cancer diagnosed incidentally by the general surgeon. CLINICAL CASE: We report the case of a 74-year-old male who accidentally swallowed his dentures while eating. After 72 h of admission to our emergency department, his clinical diagnosis was acute abdomen due to intestinal obstruction. Laparotomy was performed and revealed a stenosing mass in the left colon where the dentures were located. Pathology later reported a left colon adenocarcinoma staged as Dukes A. The patient evolved satisfactorily and is currently at 5 years without tumor activity. CONCLUSIONS: It would be useful for surgeons who are faced with an intestinal obstruction due to the accidental ingestion of a foreign body in an adult to always suspect stenosis for possible malignancy.

Obstrucción intestinal por cuerpo extraño en paciente con adenocarcinoma de colon: informe de un caso / Intestinal obstruction due to foreign body in a patient with adenocarcinoma of the colon: case report

Introducción: Cada año en todo el mundo se identifica alrededor de un millón de casos nuevos de cáncer colorrectal y medio millón de muertes. En México es la segunda neoplasia maligna gastrointestinal, después del cáncer de estómago. La sobrevida a cinco años en etapas tempranas es mayor de 90 %. No es raro el diagnóstico incidental por los cirujanos generales. El propósito de este trabajo es analizar el manejo por el cirujano general del cáncer de colon que se diagnostica incidentalmente. Caso clínico: Hombre de 74 años de edad quien ingirió accidentalmente su prótesis dental al estar comiendo; 72 horas previo al ingreso al servicio de urgencias inició con abdomen agudo por obstrucción intestinal. Por laparotomía exploradora se observó una masa estenosante en colon descendente, donde se alojó la prótesis dental; el informe de patología indicó adenocarcinoma de colon izquierdo Dukes A. El paciente evolucionó satisfactoriamente y fue integrado a un protocolo oncológico. Al momento de este informe el paciente tenía cinco años sin actividad tumoral. Conclusiones: Es conveniente que los cirujanos que se enfrentan a obstrucción intestinal por la ingestión accidental de un cuerpo extraño en la edad adulta, sospechen siempre una estenosis por posible neoplasia.

BACKGROUND: Approximately one million new cases of colorectal cancer are detected worldwide, causing about one million deaths per year. In Mexico it is the second most common gastrointestinal malignancy, after stomach cancer. The 5-year survival in early stages is > 90%. This condition is incidentally diagnosed by the general surgeon in many cases because ingestion of foreign bodies is a not uncommon condition in adults, reported more frequently in older people because of their dentures. One complication of ingestion of any foreign body is intestinal obstruction. The aim of this study is to analyze management of colon cancer diagnosed incidentally by the general surgeon. CLINICAL CASE: We report the case of a 74-year-old male who accidentally swallowed his dentures while eating. After 72 h of admission to our emergency department, his clinical diagnosis was acute abdomen due to intestinal obstruction. Laparotomy was performed and revealed a stenosing mass in the left colon where the dentures were located. Pathology later reported a left colon adenocarcinoma staged as Dukes A. The patient evolved satisfactorily and is currently at 5 years without tumor activity. CONCLUSIONS: It would be useful for surgeons who are faced with an intestinal obstruction due to the accidental ingestion of a foreign body in an adult to always suspect stenosis for possible malignancy.

Incidencia y factores que influyen en el abandono de la farmacoterapia antiepiléptica en pacientes que acuden al hospital San Juan de Dios durante los años 1990-1993 y 1er trimestre de 1994 / Incidence and factors that influence the abandonment of antepileptic drug therapy in patients who go to the hospital San Juan de Dios during the years 1990-1993 and 1st quarter of 1994

Debido al aumento peligroso de la prevalencia de pacientes que abandonan la farmacoterapia antiepiléptica, el problema se convierte en un peligro para el paciente epiléptico, quien además de sufrir nuevamente los accesos epilépticos debe correr el riesgo de lesiones incapacitantes y degenerantes en todo su sistema nervioso, es por tal motivo que el estudio trató de encontrar los posibles factores intervinientes en el abandono de la farmacoterapia antiepiléptica para poder controlarlos y así dar pautas de acción para el equipo de salud de la institución donde se realizó el estudio; sin embargo, la ubicación de los factores servirá también a todas las instituciones que trabajen con este tipo de pacientes

Incidencia y factores que influyen en el abandono de la farmacoterapia antiepiléptica en pacientes que acuden al hospital San Juan de Dios durante los años 1990-1993 y 1er trimestre de 1994 / Incidence and factors that influence the abandonment of antepileptic drug therapy in patients who go to the hospital San Juan de Dios during the years 1990-1993 and 1st quarter of 1994

Debido al aumento peligroso de la prevalencia de pacientes que abandonan la farmacoterapia antiepiléptica, el problema se convierte en un peligro para el paciente epiléptico, quien además de sufrir nuevamente los accesos epilépticos debe correr el riesgo de lesiones incapacitantes y degenerantes en todo su sistema nervioso, es por tal motivo que el estudio trató de encontrar los posibles factores intervinientes en el abandono de la farmacoterapia antiepiléptica para poder controlarlos y así dar pautas de acción para el equipo de salud de la institución donde se realizó el estudio; sin embargo, la ubicación de los factores servirá también a todas las instituciones que trabajen con este tipo de pacientes