Response of narrow QRS tachycardia in a patient with surgical closure of atrial septal defect to atrial overdrive pacing: What is the mechanism?

A 57-year old woman who had pericardial patch closure of ostium secundum atrial septal defect (ASD) at the age of 23 years presented with shortness of breath. Her echocardiogram showed no residual ASD, good biventricular function and normal pulmonary artery pressures.

Collective hydration dynamics of guanidinium chloride solutions and its possible role in protein denaturation: a terahertz spectroscopic study.

The remarkable ability of guanidinium chloride (GdmCl) to denature proteins is a well studied yet controversial phenomenon; the exact molecular mechanism is still debatable, especially the role of hydration dynamics, which has been paid less attention. In the present contribution, we have addressed the issue of whether the collective hydrogen bond dynamics of water gets perturbed in the presence of GdmCl and its possible impact on the denaturation of a globular protein human serum albumin (HSA), using terahertz (THz) time domain spectroscopy (TTDS) in the frequency range of 0.3-2.0 THz. The collective hydrogen bond dynamics is determined by fitting the obtained complex dielectric response in a multiple Debye relaxation model. To compare the results, the studies were extended to two more salts: tetramethylguanidinium chloride (TMGdmCl) and sodium chloride (NaCl). It was concluded that the change in hydration dynamics plays a definite role in the protein denaturation process.

Bridging the Gap in Cryopreservation Mechanism: Unraveling the Interplay between Structure, Dynamics, and Thermodynamics in Cryoprotectant Aqueous Solutions.

Cryoprotectants play a crucial role in preserving biological material, ensuring their viability during storage and facilitating crucial applications such as the conservation of medical compounds, tissues, and organs for transplantation. However, the precise mechanism by which cryoprotectants modulate the thermodynamic properties of water to impede the formation and growth of ice crystals, thus preventing long-term damage, remains elusive. This is evident in the use of empirically optimized recipes for mixtures that typically contain DMSO, glycerol, and various sugar constituents. Here, we use terahertz calorimetry, Overhauser nuclear polarization, and molecular dynamics simulations to show that DMSO exhibits a robust structuring effect on water around its methyl groups, reaching a maximum at a DMSO mole fraction of XDMSO = 0.33. In contrast, glycerol exerts a smaller water-structuring effect, even at higher concentrations (Scheme 1). These results potentially suggest that the wrapped water around DMSO's methyl group, which can be evicted upon ligand binding, may render DMSO a more surface-active cryoprotectant than glycerol, while glycerol may participate more as a viscogen that acts on the entire sample. These findings shed light on the molecular intricacies of cryoprotectant solvation behavior and have potentially significant implications for optimizing cryopreservation protocols.

Huntington's disease: a forensic risk factor in women.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder. Associated cognitive deficits including impulsivity and disinhibition are the same factors that also predispose to forensic risk. Men tend to be perpetrators of more severe violent behaviours than women and women are less likely than men to be arrested for violence. This finding is not applicable in the case of women with Huntington's disease and explored in the three clinical cases of women with HD and their forensic histories that are subsequently described. CASE PRESENTATION: 'A' was admitted from court following a charge of arson and reckless behavior, with increasing severity and frequency of self-harm and attempted suicide. This case demonstrates someone who had previously presented to psychiatric services on multiple occasions for various reasons, culminating in a serious criminal charge of arson due to psychiatric symptoms associated with HD.'B' was arrested and imprisoned after having been charged with actual bodily harm (ABH) for assaulting her partner and young daughter then breaking her bail conditions. Although she was gene positive for HD she had no neurological symptoms of the disease. B was given leave but needed to be recalled to hospital by police. Six weeks later the medical recommendation for a court imposed hospital order was overturned as B presented and articulated her case so convincingly in court. This case demonstrates that even in the absence of psychiatric history or movement disorder there may be substantial forensic risk indicated by subtle underlying cognitive deficits due to changes in executive function affecting the frontal lobes.'C' was admitted to acute psychiatric services after being found wandering in traffic wanting to die. She had been diagnosed with HD in the previous year and had a long criminal record on a background of alcohol dependency. Following transfer to a specialist psychiatric unit, she engaged well with a neurobehavioural levels system which rewards desirable and appropriate behaviours and she responded well to a highly structured environment resulting in discharge to a community placement. CONCLUSIONS: These three case studies aim to highlight the need to raise awareness of the increased forensic risk in women with HD. Although criminal behaviour is less frequently observed in women than men and usually violence is less severe in women, HD may cause or contribute to criminal behaviour that can be violent in nature in women who are gene carriers for HD even in the absence of movement disorder, psychiatric symptoms or overt cognitive deficits. Assessment and earlier treatment in appropriate hospital settings may successfully contain and modify behaviours leading to reduced levels of risk and recidivism in this vulnerable patient group.

Short chain polyethylene glycols unusually assist thermal unfolding of human serum albumin.

In the present study we have investigated the thermal stability of the globular transport protein human serum albumin (HSA), in the presence of two small chain polyethylene glycols (namely PEG 200 and PEG 400). Both near- and far-UV circular dichroism (CD) study reveal that addition of PEG moderately increases the α-helical content of the protein without abruptly changing its tertiary structure. The hydration structure at the protein surface experiences a notable change at 30% PEG (v/v) concentration as evidenced from compressibility and dynamic light scattering (DLS) measurements. Thermal denaturation of HSA in the presence of PEG has been studied by CD and fluorescence spectroscopy using the intrinsic fluorophore tryptophan and it has been found that addition of PEG makes the protein more prone towards unfolding, which is in contrary to what has been observed in case of larger molecular weight polymers. The energetics of the thermal unfolding process has been obtained using differential scanning calorimetry (DSC) measurements. Our study concludes that both the indirect excluded volume principle as well as interaction of the polymer at the protein surface is responsible for the observed change of the unfolding process.