Andersen-Tawil syndrome: report of 3 novel mutations and high risk of symptomatic cardiac involvement.

IntroductionAndersen-Tawil syndrome (ATS) is a potassium channelopathy affecting cardiac and skeletal muscle. Periodic paralysis is a presenting symptom in some patients, whereas, in others, symptomatic arrhythmias or prolongation of QT in echocardiographic recordings will lead to diagnosis of ATS. Striking intrafamilial variability of expression of KCNJ2 mutations and rarity of the syndrome may lead to misdiagnosis.MethodsWe report 15 patients from 8 Polish families with ATS, including 3 with novel KCNJ2 mutations.ResultsAll patients had dysmorphic features; periodic paralysis affected males more frequently than females (80% vs. 20%), and most attacks were normokalemic. Two patients (with T75M and T309I mutations) had aborted sudden cardiac death. An implantable cardioverter-defibrillator was utilized in 40% of cases.ConclusionsKCNJ2 mutations cause a variable phenotype, with dysmorphic features seen in all patients studied, a high penetrance of periodic paralysis in males and ventricular arrhythmia with a risk of sudden cardiac death

The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) represent the most common heritable neuromuscular disorders. Molecular diagnostics of CMT1A/HNPP diseases confirm clinical diagnosis, but their value is limited to the clinical course and prognosis. However, no biomarkers of CMT1A/HNPP have been identified. We decided to explore if the LITAF/SIMPLE gene shared a functional link to the PMP22 gene, whose duplication or deletion results in CMT1A and HNPP, respectively. By studying a large cohort of CMT1A/HNPP-affected patients, we found that the LITAF I92V sequence variant predisposes patients to an earlier age of onset of both the CMT1A and HNPP diseases. Using cell transfection experiments, we showed that the LITAF I92V sequence variant partially mislocalizes to the mitochondria in contrast to wild-type LITAF which localizes to the late endosome/lysosomes and is associated with a tendency for PMP22 to accumulate in the cells. Overall, this study shows that the I92V LITAF sequence variant would be a good candidate for a biomarker in the case of the CMT1A/HNPP disorders

Variance of the Casimir force in an ideal Bose gas

We consider an ideal Bose gas enclosed in a $d$-dimensional slab of thickness $D$. Using the grand canonical ensemble we calculate the variance of the thermal Casimir force acting on the slab's walls. The variance evaluated per unit wall area is shown to decay like $\Delta_{var}/D$ for large $D$. The amplitude $\Delta_{var}$ is a non-universal function of two scaling variables $\lambda/ \xi$ and $D/ \xi$, where $\lambda$ is the thermal de Broglie wavelength and $\xi$ is the bulk correlation length. It can be expressed via the bulk pressure, the Casimir force per unit wall area, and its derivative with respect to chemical potential. For thermodynamic states corresponding to the presence of the Bose-Einstein condensate the amplitude $\Delta_{var}$ retains its non-universal character while the ratio of the mean standard deviation and the Casimir force takes the scaling form $(D/L)^{\frac{d-1}{2}}\, (D/\lambda)^{d/2}$, where $L$ is the linear size of the wall.Comment: 9 pages, no figure

Effective binding potential from Casimir interactions: the case of the Bose gas

We consider the thermal Casimir effect in ideal Bose gases, where the dispersion relation involves both terms quadratic and quartic in momentum. We demonstrate that if macroscopic objects are immersed in such a fluid in spatial dimensionality $d\in\{3,7, 11, \dots\}$ and at the critical temperature $T_c$, the Casimir force acting between them is characterized by a sign which depends on the separation $D$ between the bodies and changes from attractive at large distances to repulsive at smaller separations. In consequence, an effective potential which binds the two objects at a finite separation arises. We demonstrate that for odd integer dimensionality $d\in \{3, 5, 7, \dots\}$, the Casimir energy is a polynomial of degree $(d-1)$ in $D^{-2}$. We point out a very special role of dimensionality $d=3$, where we derive a strikingly simple form of the Casimir energy as a function of $D$ at Bose-Einstein condensation. We discuss crossover between monotonous and oscillatory decay of the Casimir interaction above the condensation temperature

The use of anticoagulants in morbidly obese patients

Due to its constantly growing incidence, obesity is an increasingly serious social and medical problem. Available data on the use of novel oral anticoagulants in morbidly obese and obese patients are very limited. However, we tried to summarize the available knowledge on the use of anticoagulants in this subpopulation of patients in everyday clinical practice. Studies on the clinical use of anticoagulants provide a poor basis for any adjustment of doses in obese patients as compared to patients with normal body weight. In our opinion, further studies are required in this particular population

Postępowanie terapeutyczne w miastenii

Miastenia jest autoimmunologiczną chorobą złącza nerwowo--mięśniowego, której przebieg kliniczny charakteryzuje dużazmienność objawów. Nasilenie objawów waha się od łagodnychobjawów ocznych, po zagrażający życiu stan, jakim jest przełommiasteniczny. Na miastenię choruje w Polsce około 6000 pacjentów,od wczesnego dzieciństwa do późnej starości. Prawidłowoleczona miastenia jest chorobą o dobrym rokowaniu dla ponad90% pacjentów. Decyzje terapeutyczne powinny uwzględniaćnasilenie objawów klinicznych, obecność patologii grasicy orazwiek i inne problemy zdrowotne pacjenta