Wilson's disease presenting as isolated obsessive-compulsive disorder

Wilson's disease (WD) is a genetic neurodegenerative disorder; it exhibits wide heterogeneity in symptoms and usually presents with liver disease and/ or neuropsychiatric manifestations. The common neurological manifestations observed are dysarthria, gait disturbance, dystonia, rigidity, tremor, dysphagia and chorea. The frequent psychiatric manifestations reported are personality and mood changes, depression, phobias, cognitive impairment, psychosis, anxiety, compulsive and impulsive behavior. Isolated obsessive-compulsive disorder (OCD) is a rare presentation of WD. Reported herein is a case of a 17-year-old boy with isolated OCD. He presented to the psychiatrist with symptoms of contamination obsessions and washing compulsions, along with compulsion of repeated feet tapping and was treated with adequate doses of fluoxetine for 6 months but did not improve. Later on, he was diagnosed as a case of WD and showed improvement with chelating and behavior therapy. This implies the importance of the occurrence of isolated psychological symptoms in WD.     

Enterobacter sakazakii in infants: novel phenomenon in India

E. sakazakii has been implicated in necrotizing enterocolitis, bloodstream and central nervous system infections, with mortality rates of 40-80%. Two cases of E. sakazakii infections; one preterm very low birth weight neonate with meningitis and a two month infant with bacteraemia, are described for the first time in India. The first baby succumbed to the infection while the other responded to appropriate therapy. Powdered infant milk formulae have been implicated in causing neonatal infections and the first baby was on formula feed with classic signs of sepsis and meningitis. The second infant was on breast feed and probably developed nosocomial E. sakazakii bacteraemia.     

Species differences in bile acids II. Bile acid metabolism

One of the mechanisms of drug‐induced liver injury (DILI) involves alterations in bile acid (BA) homeostasis and elimination, which encompass several metabolic pathways including hydroxylation, amidation, sulfation, glucuronidation and glutathione conjugation. Species differences in BA metabolism may play a major role in the failure of currently used in vitro and in vivo models to predict reliably the DILI during the early stages of drug discovery and development. We developed an in vitro cofactor‐fortified liver S9 fraction model to compare the metabolic profiles of the four major BAs (cholic acid, chenodeoxycholic acid, lithocholic acid and ursodeoxycholic acid) between humans and several animal species. High‐ and low‐resolution liquid chromatography–tandem mass spectrometry and nuclear magnetic resonance imaging were used for the qualitative and quantitative analysis of BAs and their metabolites. Major species differences were found in the metabolism of BAs. Sulfation into 3‐O‐sulfates was a major pathway in human and chimpanzee (4.8%–52%) and it was a minor pathway in all other species (0.02%–14%). Amidation was primarily with glycine (62%–95%) in minipig and rabbit and it was primarily with taurine (43%–81%) in human, chimpanzee, dog, hamster, rat and mice. Hydroxylation was highest (13%–80%) in rat and mice followed by hamster, while it was lowest (1.6%–22%) in human, chimpanzee and minipig. C6‐β hydroxylation was predominant (65%–95%) in rat and mice, while it was at C6‐α position in minipig (36%–97%). Glucuronidation was highest in dog (10%–56%), while it was a minor pathway in all other species (<12%). The relative contribution of the various pathways involved in BA metabolism in vitro were in agreement with the observed plasma and urinary BA profiles in vivo and were able to predict and quantify the species differences in BA metabolism. In general, overall, BA metabolism in chimpanzee is most similar to human, while BA metabolism in rats and mice is most dissimilar from human.     

Hollow Microparticles as a Superior Delivery System over Solid Microparticles for the Encapsulation of Peptides

Purpose

Peptides are gaining significant interests as therapeutic agents due to their high targeting specificity and potency. However, their low bioavailability and short half-lives limit their massive potential as therapeutics. The use of dense, solid particles of biodegradable polymer as a universal carrier for peptides also has its challenges, such as inefficient peptide release and low bioactivity. In this paper, it was established that hollow microparticles (h-MPs) instead of solid microparticles (s-MPs), as peptide carriers, could improve the release efficiency, while better preserving their bioactivity.

Methods

Glucagon like Peptide-1 (GLP-1) was encapsulated as a model peptide. Mass loss, average molecular weight changes, intraparticle pH, polymer-peptide interaction and release studies, together with bioactivity assessment of the peptide for s-MPs and h-MPs were systematically analyzed and evaluated for efficacy.

Results

The intraparticle pH of s-MPs was as low as 2.64 whereas the pH of h-MPs was 4.99 by day 7. Consequently, 93% of the peptide extracted from h-MPs was still bioactive while only 58% of the peptide extracted from s-MPs was bioactive. Likewise, the cumulative release of GLP-1 by day 14 from h-MPs showed a cumulative amount of 88?±?8% as compared to 33?±?6% for s-MPs.

Conclusions

The cumulative release of peptide can be significantly improved, and the bioactivity can be better preserved by simply using h-MPs instead of s-MPs as carriers.

     

Case report of a uniocular topography guided laser-assisted in situ keratomileusis enhancement following an incorrectly treated astigmatic axis

A 23-year-old male presented to us wanting spectacle removal for cosmetic purposes. He underwent bilateral wavefront optimized (WFO) laser-assisted in situ keratomileusis (LASIK) on the Alcon Wavelight^® EX-500 excimer laser with an incorrectly treated astigmatism axis for left eye due to a manual data entry error in the laser. WFO LASIK treats the sphere and cylinder only. LASIK enhancement with topographic-guided ablation resulted in the elimination of all refractive errors and gave excellent results. Wavelight^® topographic-guided treatment can perform two separate layers of correction in the same ablation: The first is to treat the corneal irregularities for the higher order aberration (HOA) removal, the second one meant to treat the sphere and cylinder if indicated.     

The association between sleep duration,napping, and stroke stratified by self-health status among Chinese people over 65 years old from the China health and retirement longitudinal study

Purpose

Stroke is a major cause of death in China. This study aimed to investigate the association between sleep duration (nighttime sleep and daytime napping) and stroke in elderly Chinese individuals with self-reported health status.

Methods

A total of 4785 Chinese adults over 65 years from the 2011 China Health and Retirement Longitudinal Study (CHARLS) were included. Binary logistic regression was used to estimate odds ratios and 95% confidence intervals of the association between sleep duration and stroke stratified by self-reported health status.

Results

A significant association between short sleep duration (< 7 h per day) and the risk of stroke (aOR?=?2.05; 95% CI 1.31–3.19), after controlling for sociodemographic characteristics, lifestyle factors, health status, and comorbidities. There was no significant association between short and long sleep duration and stroke in the individuals who reported good general health status. However, in individuals who reported poor health status, short sleep duration (aOR?=?2.11; 95% CI 1.30–3.44) and long sleep duration (aOR?=?1.86; 95% CI 1.08–3.21) were significantly associated with increased risk of stroke, compared with normal sleep duration (7–8 h per day). Disability was significantly associated with stroke in both self-reported good and poor health groups. Rural residence was significantly associated with a lower risk of stroke among individuals who reported poor health status.

Conclusions

Both short and long sleep duration were significantly associated with stroke among individuals who reported poor health. Stroke prevention should be focused on elderly individuals who believe that they have health problems.

     

Catastrophic Systemic Embolization from a Left Atrial Myxoma

We report the fatal course of a left atrial myxoma: its systemic embolization to the coronary, cerebral, renal, and peripheral vascular beds in a 39-year-old woman resulted in rapid clinical deterioration, multiorgan failure, and death. Among reported cases of left atrial myxoma, this degree of embolic burden is exceedingly rare. In addition to reporting the patient''s case, we discuss the presentation and diagnosis of possible intracardiac sources of systemic emboli.Key words: Cerebral arteries/pathology, embolism/diagnosis, fatal outcome, heart atria/pathology, heart neoplasms/complications, myocardial infarction/etiology, myxoma/complications/diagnosis/epidemiology/pathologyWhen a patient presents with simultaneous vascular insults that involve multiple organ systems, a catastrophic clinical outcome can result. We report the case of a patient who had symptoms of systemic embolization, and we discuss the presentation, recognition, and treatment of the left atrial myxoma that was responsible.     

Defining and managing patients with non-ST-elevation myocardial infarction: Sorting through type 1 vs other types

Advances in cardiovascular (CV) imaging, redefined electrocardiogram criteria, and high-sensitivity CV biomarker assays have enabled more differentiated etiological classification of myocardial infarction (MI). Type 1 MI has a different underlying pathophysiology than type 2 through type 5 MI; type 1 MI is characterized primarily by intracoronary atherothrombosis and the other types by a variety of mechanisms, which can occur with or without an atherosclerotic component. In type 2 MI, there is evidence of myocardial oxygen supply-demand imbalance unrelated to acute coronary atherothrombosis. Types 1 and 2 MI are spontaneous events, while type 4 and type 5 are procedure-related; type 3 MI is identified only after death. Most type 1 and type 2 MI present as non-ST-elevation MI (NSTEMI), although both types can also present as ST-elevation MI. Because of their different underlying etiologies, type 1 and type 2 NSTEMI have different presentation and prognosis and should be managed differently. In this article, we discuss the epidemiology, prognosis, and management of NSTEMI occurring in the setting of underlying type 1 or type 2 pathophysiology. Most NSTEMI (65%–90%) are type 1 MI. Patients with type 2 MI have multiple comorbidities and causes of in-hospital mortality among these patients are not always CV-related. It is important to distinguish between type 1 and type 2 NSTEMI early in the clinical course to allow for the use of the most appropriate treatments that will provide the greatest benefit for these patients.