Gitelman syndrome

Gitelman syndrome (GS), also referred to as familial hypokalemia-hypomagnesemia, is characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and low urinary calcium excretion. The prevalence is estimated at approximately 1:40,000 and accordingly, the prevalence of heterozygotes is approximately 1% in Caucasian populations, making it one of the most frequent inherited renal tubular disorders. In the majority of cases, symptoms do not appear before the age of six years and the disease is usually diagnosed during adolescence or adulthood. Transient periods of muscle weakness and tetany, sometimes accompanied by abdominal pain, vomiting and fever are often seen in GS patients. Paresthesias, especially in the face, frequently occur. Remarkably, some patients are completely asymptomatic except for the appearance at adult age of chondrocalcinosis that causes swelling, local heat, and tenderness over the affected joints. Blood pressure is lower than that in the general population. Sudden cardiac arrest has been reported occasionally. In general, growth is normal but can be delayed in those GS patients with severe hypokalemia and hypomagnesemia

The long-term course of shoulder complaints:a prospective study in general practice

Objective. Assessment of the long-term course of shoulder complaints in patients in general practice with special focus on changes in diagnostic category and fluctuations in the severity of the complaints. Design. Prospective descriptive study. Setting. Four general practices in The Netherlands. Method. All patients (101) with shoulder complaints seen in a 5 month period were included. Assessment took place 26 weeks and 12-18 months after inclusion in the study with a pain questionnaire and a physical examination. Results. A total of 51% of the patients experienced (mostly recurrent) complaints after 26 weeks and 41% after 12-18 months. Diagnostic changes were found over the course of time, mostly from synovial disorders towards functional disorders of the structures of the shoulder girdle, but also the other way round. Although 52 of the 101 patients experienced complaints in week 26, 62% of those patients considered themselves 'cured'. After 12-18 months, 51% of the 39 patients experiencing complaints felt 'cured'. Conclusion. Many patients seen with shoulder complaints in general practice have recurrent complaints. The nature of these complaints varies considerably over the course of time, leading to changes in diagnostic category. Because of the fluctuating severity of the complaints over time, feeling 'cured' or not 'cured' is also subject to change over time

Till death (or an intruder) do us part: intrasexual-competition in a monogamous Primate

Polygynous animals are often highly dimorphic, and show large sex-differences in the degree of intra-sexual competition and aggression, which is associated with biased operational sex ratios (OSR). For socially monogamous, sexually monomorphic species, this relationship is less clear. Among mammals, pair-living has sometimes been assumed to imply equal OSR and low frequency, low intensity intra-sexual competition; even when high rates of intra-sexual competition and selection, in both sexes, have been theoretically predicted and described for various taxa. Owl monkeys are one of a few socially monogamous primates. Using long-term demographic and morphological data from 18 groups, we show that male and female owl monkeys experience intense intra-sexual competition and aggression from solitary floaters. Pair-mates are regularly replaced by intruding floaters (27 female and 23 male replacements in 149 group-years), with negative effects on the reproductive success of both partners. Individuals with only one partner during their life produced 25% more offspring per decade of tenure than those with two or more partners. The termination of the pair-bond is initiated by the floater, and sometimes has fatal consequences for the expelled adult. The existence of floaters and the sporadic, but intense aggression between them and residents suggest that it can be misleading to assume an equal OSR in socially monogamous species based solely on group composition. Instead, we suggest that sexual selection models must assume not equal, but flexible, context-specific, OSR in monogamous species.Wenner-Gren Foundation, L.S.B. Leakey Foundation, the National Geographic Society, National Science Foundation (BCS- 0621020), the University of Pennsylvania Research Foundation and the Zoological Society of San Diego, German Science Foundation (HU 1746-2/1

Hybrid modeling of biological networks: mixing temporal and qualitative biological properties

<p>Abstract</p> <p>Background</p> <p>Modeling a dynamical biological system is often a difficult task since the a <it>priori </it>unknown parameters of such models are not always directly given by the experiments. Despite the lack of experimental quantitative knowledge, one can see a dynamical biological system as (i) the combined evolution tendencies (increase or decrease) of the biological compound concentrations, and: (ii) the temporal features, such as delays between two concentration peaks (i.e. the times when one of the components completes an increase (resp. decrease) phase and starts a decrease (resp. increase) phase).</p> <p>Results</p> <p>We propose herein a new hybrid modeling framework that follows such biological assumptions. This hybrid approach deals with both a qualitative structure of the system and a quantitative structure. From a theoretical viewpoint, temporal specifications are expressed as equality or inequality constraints between delay parameters, while the qualitative specifications are expressed as an ordered pattern of the concentrations peaks of the components. Using this new hybrid framework, the temporal specifications of a biological system can be obtained from incomplete experimental data. The model may be processed by a hybrid model-checker (e.g. Phaver) which is able to give some new constraints on the delay parameters (e.g. the delay for a given transition is exactly 5 hours after the later peak of a gene product concentration). Furthermore, by using a constraint solver on the previous results, it becomes possible to get the set of parameters settings which are consistent with given specifications. Such a modeling approach is particularly accurate for modeling oscillatory biological behaviors like those observed in the Drosophila circadian cycles. The achieved results concerning the parameters of this oscillatory system formally confirm the several previous studies made by numerical simulations. Moreover, our analysis makes it possible to propose an automatic investigation of the respective impact of per and tim on the circadian cycle.</p> <p>Conclusions</p> <p>A new hybrid technique for an automatic formal analysis of biological systems is developed with a special emphasis on their oscillatory behaviors. It allows the use of incomplete and empirical biological data.</p

Expression of the SST receptor 2 in uveal melanoma is not a prognostic marker

Introduction: Uveal melanoma (UM) cells and neurohormone-producing cells both originate from the neural crest. Somatostatin receptors subtype 2 (SSTR2) are over-expressed in several tumors, often from neuroendocrine origin, and synthetic antagonists like octreotide and octreotate are being used as diagnostic or therapeutic agents. We investigated the SSTR2 expression in UM, and determined whether this expression was related to prognosis of the disease. Materials and methods: UM cell lines and fresh primary UM samples were tested for SSTR2 expression by autoradiography (AR) using 125I-Tyr3-octreotate. Furthermore, UM cell lines were analyzed for SSTR2 mRNA expression with quantitative real-time RT-PCR. Results: Using AR, cell-surface SSTR2 expression was demonstrated in two UM metastatic cell lines, but no expression was detected in three cell lines derived from primary UM. However, all primary and metastatic UM cell lines showed mRNA expression levels for SSTR2 using quantitative real-time RT-PCR. Only three of 14 primary UM demonstrated moderate SSTR2 expression, and this expression was not significantly associated with tumor-free survival or any tested prognostic factor. Conclusions: Based on the rare and low expression of SSTR2 found in primary UM specimens and in UM cell lines, we conclude that SSTR2 is not widely expressed in UM. Furthermore, SSTR2 expression was not associated with tumor-free survival and prognostic factors. Therefore SSTR2 is not suited as prognostic marker or therapeutic target in UM

Comparative genomic analysis of two emergent human adenovirus type 14 respiratory pathogen isolates in China reveals similar yet divergent genomes

Human adenovirus type 14 (HAdV-B14p) was originally identified as an acute respiratory disease (ARD) pathogen in The Netherlands in 1955. For approximately fifty years, few sporadic infections were observed. In 2005, HAdV-B14p1, a genomic variant, re-emerged and was associated with several large ARD outbreaks across the U.S. and, subsequently, in Canada, the U.K., Ireland, and China. This strain was associated with an unusually higher fatality rate than previously reported for both this prototype and other HAdV types in general. In China, HAdV-B14 was first observed in 2010, when two unrelated HAdV-B14-associated ARD cases were reported in Southern China (GZ01) and Northern China (BJ430), followed by three subsequent outbreaks. While comparative genomic analysis, including indel analysis, shows that the three China isolates, with whole genome data available, are similar to the de Wit prototype, all are divergent from the U.S. strain (303600; 2007). Although the genomes of strains GZ01 and BJ430 are nearly identical, as per their genome type characterization and percent identities, they are subtly divergent in their genome mutation patterns. These genomes indicate possibly two lineages of HAdV-B14 and independent introductions into China from abroad, or subsequent divergence from one; CHN2012 likely represents a separate sub-lineage. Observations of these simultaneously reported emergent strains in China add to the understanding of the circulation, epidemiology, and evolution of these HAdV pathogens, as well as provide a foundation for developing effective vaccines and public health strategies, including nationwide surveillance in anticipation of larger outbreaks with potentially higher fatality rates associated with HAdV-B14p1