Decoding muscle-resident Schwann cell dynamics during neuromuscular junction remodeling.

Understanding neuromuscular junction (NMJ) repair mechanisms is essential for addressing degenerative neuromuscular conditions. Here, we focus on the role of muscle-resident Schwann cells in NMJ reinnervation. In young Sod1-/- mice, a model of progressive NMJ degeneration, we identified a clear NMJ 'regenerative window' that allowed us to define regulators of reinnervation and crossing Sod1-/- mice with S100GFP-tg mice permitted visualization and analysis of Schwann cells. High-resolution imaging and single-cell RNA sequencing provide a detailed analysis of Schwann cell number, morphology, and transcriptome revealing multiple subtypes, including a previously unrecognized terminal Schwann cell (tSC) population expressing a synapse promoting signature. We also discovered a novel SPP1-driven cellular interaction between myelin Schwann cells and tSCs and show that it promotes tSC proliferation and reinnervation following nerve injury in wild type mice. Our findings offer important insights into molecular regulators critical in NMJ reinnervation that are mediated through tSCs to maintain NMJ function.

The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population.

The objective of this study is to estimate the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants and their contribution to warfarin dose variability in Qataris. One hundred and fifty warfarin-treated Qatari patients on a stable dose and with a therapeutic INR for at least three consecutive clinic visits were recruited. Saliva samples were collected using Oragene DNA self-collection kit, followed by DNA purification and genotyping via TaqMan Real-Time-PCR assay. The population was stratified into derivation and validation cohorts for the dosing model. The minor allele frequency (MAF) of VKORC1 (-1639G>A) was A (0.47), while the MAF's for the CYP2C9*2 and *3 and CYP4F2*3 were T (0.12), C (0.04) and T (0.43), respectively. Carriers of at least one CYP2C9 decreased function allele (*2 or *3) required lower median (IQR) warfarin doses compared to noncarriers [24.5 (14.5) mg/week vs. 35 (21) mg/week, p < 0.001]. Similarly, carriers of each additional copy of (A) variant in VKORC1 (-1639G>A) led to reduction in warfarin dose requirement compared to noncarriers [21(7.5) vs. 31.5(18.7) vs. 43.7(15), p < 0.0001]. CYP4F2*3 polymorphism on the other hand was not associated with warfarin dose. Multivariate analysis on the derivation cohort (n = 104) showed that a dosing model consisting of hypertension (HTN), heart failure (HF), VKORC1 (-1639G>A), CYP2C9*2 & *3, and smoking could explain 39.2% of warfarin dose variability in Qataris (P < 0.001). In the validation cohort (n = 45), correlation between predicted and actual warfarin doses was moderate (Spearman's rho correlation coefficient = 0.711, p < 0.001). This study concluded that VKORC1 (-1639G>A), CYP2C9*2 & *3 are the most significant predictors of warfarin dose along with HTN, HF and smoking.

INTERVENTION PROGRAM FOR NURSING STAFF REGARDING APPROACH TO A PATIENT WITH SPIDER PHOBIA AND/OR BITE.

Spider bites are uncommon medical events, since there are limited number of spiders world-wide with fangs strong enough to pierce human skin, and most spiders bite humans only as a final defense when being crushed between skin and another object. Thus, most lesions attributed to spider bites are caused by some other etiology. The spiders that can cause medically significant bites include widow and false widow spiders (worldwide), recluse spiders (mostly North and South America), Australian funnel web spiders (eastern coastal Australia) and Phoneutria spiders (Brazil). Acute spider bites most commonly result in a solitary papule, pustule, or wheal. Systemic symptoms can accompany envenomation of widow; funnel web, and Phoneutria spiders, and less often, those of recluse spiders.

OCCUPATIONAL, NOSOCOMIAL OR HOSPITAL ACQUIRED TOXOPLASMOSIS.

Toxoplasma gondii is protozoan parasite infects wild and domestic animals including birds, cats, sheep, goats, cattle, pigs and poultry. Cats are the definitive host of Toxoplasma and transmitted to other animals or people. There are three forms of T gondii: the tachyzoite (the rapidly reproducing form), the bradyzoite (a slower reproducing form contained in tissue cysts), and the sporozoite (contained in oocysts). The tachyzoite invade cells in the body where it thep multiplies rapidly and can destroy cells. When the cells die, the tachyzoites are released and infect other cells. For this reason, tachyzoites are seen in many tissues and organs throughout the body that are infected during this acute phase of the disease. This is also called the extraintestinal phase of the infection since it can affect all cells outside the intestines in all infected animals. However, only cats have the. intestinal phase of the infection. Two or three weeks after the first infection, the Toxoplasma divides more slowly and a protective membrane forms around the parasite cells. The cyst containing the parasites is called a zoitocyst and the cells inside the cyst are called bradyzoites. The tissue cysts are formed primarily in brain, eye, heart muscle, and skeletal muscle. Bradyzoites persist in tissues for many years, possibly for the life of the host. In cats, Toxoplasma infects the small intestine lining where they reproduce asexually. After a few days of rapid reproduction the cells transform into a sexual form, combine, and become enclosed in a cyst called an oocyst. Oocysts contain the sporozoite form of the Toxoplasma parasite. Gocysts are found in both wild and domestic cats but not in any other animals or birds.

PROTOZOA CAUSING FOOD POISONING.

Food poisoning also called foodbome illness, or illness caused by eating contaminated food is a term used to cover an unpleasant range of illnesses. Food poisoning symptoms vary with the source of contamination. Most types of food poisoning cause one or more of the following signs and symptoms: nausea, vomiting, watery diarrhea, abdominal pain and cramps and fever Signs and symptoms may start within hours after eating the contaminated food, or they may begin days or even weeks later. Sickness caused by food poisoning generally lasts from a few hours to several days.