Measuring Subvisible Particles in Protein Formulations Using a Modified Light Obscuration Sensor with Improved Detection Capabilities.

Although light obscuration is the "gold standard" for subvisible particle measurements in biopharmaceutical products, the current technology has limitations with respect to the detection of translucent proteinaceous particles and particles of sizes smaller and around 2 μm. Here, we describe the evaluation of a modified light obscuration sensor utilizing a novel measuring mode. Whereas standard light obscuration methodology monitors the height (amplitude) of the signal, the new approach monitors its length (width).

Freeze drying of L-arginine/sucrose-based protein formulations, part I: influence of formulation and arginine counter ion on the critical formulation temperature, product performance and protein stability.

The objective of this study was to investigate product performance of freeze dried l-arginine/sucrose-based formulations under variation of excipient weight ratios, l-arginine counter ions and formulation pH as a matrix to stabilize a therapeutic monoclonal antibody (MAb) during freeze drying and shelf life. Protein and placebo formulations were lyophilized at aggressive primary drying conditions and key attributes of the freeze dried solids were correlated to their thermal properties and critical formulation temperature. Stability (physical) during processing and long-term storage of the MAb in different formulations was assessed by SE-HPLC.

A CB2-Selective Cannabinoid Suppresses T-Cell Activities and Increases Tregs and IL-10.

We have previously shown that agonists selective for the cannabinoid receptor 2 (CB2), including O-1966, inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ graft rejection, predominantly through effects on T-cells. Current studies explored the mechanism of this immunosuppression by O-1966 using mouse spleen cells. Treatment with O-1966 dose-relatedly decreased levels of the active nuclear forms of the transcription factors NF-κB and NFAT in wild-type T-cells, but not T-cells from CB2 knockout (CB2R k/o) mice.

Accelerated intoxication of GABAergic synapses by botulinum neurotoxin A disinhibits stem cell-derived neuron networks prior to network silencing.

Botulinum neurotoxins (BoNTs) are extremely potent toxins that specifically cleave SNARE proteins in peripheral synapses, preventing neurotransmitter release. Neuronal responses to BoNT intoxication are traditionally studied by quantifying SNARE protein cleavage in vitro or monitoring physiological paralysis in vivo. Consequently, the dynamic effects of intoxication on synaptic behaviors are not well-understood.

'Carriers of variant luteinizing hormone (V-LH) among 1593 Baltic men have significantly higher serum LH'.

Luteinizing hormone (LH) is a pituitary heterodimeric glycoprotein essential in male and female reproduction. Its functional polymorphic variant (V-LH) is determined by two missense mutations (rs1800447, A/G, Trp8Arg; rs34349826, A/G, Ile15Thr) in the LH β-subunit encoding gene (LHB; 19q13.3; 1111 bp; 3 exons).

Upper gastrointestinal fluoroscopic simulator for neonates with bilious emesis.

Prompt diagnosis of malrotation and midgut volvulus in infants with bilious emesis is critical. However because of the limited frequency of pediatric upper gastrointestinal (UGI) fluoroscopic procedures in neonates, many diagnostic radiology residents complete their training never having seen or performed a UGI on a baby for evaluation of malrotation and midgut volvulus. A UGI simulation model for infants with bilious emesis was created to supplement the hands-on fluoroscopic experience of residents in training.

A non-interventional phase IV Belgian survey to assess the antiviral effectiveness of pegylated interferon-alpha-2b and ribavirin treatment according to the stage of liver fibrosis in previously untreated patients with genotype 1/4/5/6 chronic hepatitis C (PRACTICE).

Background And Study Aims: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC.

Patients And Methods: 538 patients treated with pegylated interferon alfa 2b 1.

Effect of carbetocin, oxytocin and prostaglandin E2 and F2α on intrauterine pressure in cows in dioestrus and oestrus.

Objective: To describe the physiological activity of the myometrium in oestrus and dioestrus and the induced activity after medication in cows with particular reference to segmental differences.

Material And Methods: Six cows were given the pharmaceuticals carbetocin, oxytocin and prostaglandin (PG) F2α (dinoprost) intramuscularly and PGE2 intravenously. The physiological myometrial activity was recorded for 15 minutes and the induced activity for 105 minutes by using a transcervically attached pressure probe containing six pressure microtransducers.

[Thrombotic thrombocytopenic purpura--an often missed diagnosis].

Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by mechanical anemia with fragmentation of red blood cells and thrombocytopenia by consumption. The physiopathology has been extensively studied and a severe deficiency of ADAMTS 13, proteolytic enzyme of von Willebrand factor (vWF), has been shown to be responsible for its manifestation. We stress the importance of visual blood smear examination when clinical and hematological features of TTP are present, as it seems to be under-diagnosed, especially in infants and young adults.

Factors associated with mode of transport decision making for pediatric-neonatal interfacility transport.

Objective: Transport professionals must routinely engage in complex decision making. One challenging decision is the determination of mode of transport. This study explores the decisional factors involved in the determination of mobilizing ground ambulance versus helicopter for pediatric-neonatal interfacility transport.

Functional and structural alterations in the cingulate motor area relate to decreased fronto-striatal coupling in major depressive disorder with psychomotor disturbances.

Psychomotor disturbances are a classic feature of major depressive disorders. These can manifest as lack of facial expressions and decreased speech production, reduced body posture and mobility, and slowed voluntary movement. The neural correlates of psychomotor disturbances in depression are poorly understood but it has been suggested that outputs from the cingulate motor area (CMA) to striatal motor regions, including the putamen, could be involved.

Application of RNA interference to improve mechanistic understanding of omics responses to a hepatotoxic drug in primary rat hepatocytes.

Inhibition of the glucagon receptor (GCGR) has been identified as a potential therapeutic approach for the treatment of type 2 diabetes. However, a small molecule drug candidate antagonizing GCGR (BAY16) failed during preclinical drug development, in part due to drug induced hepatotoxicity in animals. Since there is evidence to suggest that endogenous GCGR signaling might be important for hepatocyte survival, we hypothesized that on-target effects, i.

Perception of CPR quality: Influence of CPR feedback, Just-in-Time CPR training and provider role.

Aim: Many healthcare providers rely on visual perception to guide cardiopulmonary resuscitation (CPR), but little is known about the accuracy of provider perceptions of CPR quality. We aimed to describe the difference between perceived versus measured CPR quality, and to determine the impact of provider role, real-time visual CPR feedback and Just-in-Time (JIT) CPR training on provider perceptions.

Methods: We conducted secondary analyses of data collected from a prospective, multicenter, randomized trial of 324 healthcare providers who participated in a simulated cardiac arrest scenario between July 2012 and April 2014.

A major pain in the … Back and epigastrium: an unusual case of spontaneous celiac artery dissection.

A 60-year-old woman with mitral valve prolapse, chronic low back pain, and a 30-pack year smoking history presented for a second admission of poorly controlled mid-back pain 10 days after her first admission. She had concomitant epigastric pain, sharp/burning in quality, radiating to the right side and to the mid-back, not associated with food nor improving with pain medications. She denied nausea, vomiting, diarrhea, constipation, dark stools, or blood per rectum.

Auditory Behavior in Everyday Life (ABEL) questionnaire in Hebrew and in Arabic and its association with clinical tests in cochlear-implanted children.

Background: The aim of this study was to describe the results of the Auditory Behavior in Everyday Life (ABEL) questionnaire adapted to Hebrew and to Arabic and its association to clinical test results in children with cochlear implants. As assessment of hearing by audiometry does not always adequately reflect performance in daily life, questionnaires have been developed to assess functioning in natural surroundings and to track progress. In order to evaluate cochlear-implanted children's verbal and communicative abilities, the parental ABEL questionnaire was developed in 2002.

Silver resistance genes are overrepresented among Escherichia coli isolates with CTX-M production.

Members of the Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs) of the CTX-M type have disseminated rapidly in recent years and have become a threat to public health. In parallel with the CTX-M type expansion, the consumption and widespread use of silver-containing products has increased. To determine the carriage rates of silver resistance genes in different Escherichia coli populations, the presence of three silver resistance genes (silE, silP, and silS) and genes encoding CTX-M-, TEM-, and SHV-type enzymes were explored in E.

Logarithmic and power law input-output relations in sensory systems with fold-change detection.

Two central biophysical laws describe sensory responses to input signals. One is a logarithmic relationship between input and output, and the other is a power law relationship. These laws are sometimes called the Weber-Fechner law and the Stevens power law, respectively.

Patient Handoffs: Is Cross Cover or Night Shift Better?

Objectives: Studies show singular handoffs between health care providers to be risky. Few describe sequential handoffs or compare handoffs from different provider types. We investigated the transfer of information across 2 handoffs using a piloted survey instrument.

Widespread sequence variations in VAMP1 across vertebrates suggest a potential selective pressure from botulinum neurotoxins.

Botulinum neurotoxins (BoNT/A-G), the most potent toxins known, act by cleaving three SNARE proteins required for synaptic vesicle exocytosis. Previous studies on BoNTs have generally utilized the major SNARE homologues expressed in brain (VAMP2, syntaxin 1, and SNAP-25). However, BoNTs target peripheral motor neurons and cause death by paralyzing respiratory muscles such as the diaphragm.