RyR1 Deficiency in Congenital Myopathies Disrupts Excitation–Contraction Coupling

In skeletal muscle, excitation–contraction (EC) coupling is the process whereby the voltage‐gated dihydropyridine receptor (DHPR) located on the transverse tubules activates calcium release from the sarcoplasmic reticulum by activating ryanodine receptor (RyR1) Ca²⁺ channels located on the terminal cisternae. This subcellular membrane specialization is necessary for proper intracellular signaling and any alterations in its architecture may lead to neuromuscular disorders. In this study, we present evidence that patients with recessive RYR1‐related congenital myopathies due to primary RyR1 deficiency also exhibit downregulation of the alfa 1 subunit of the DHPR and show disruption of the spatial organization of the EC coupling machinery. We created a cellular RyR1 knockdown model using immortalized human myoblasts transfected with RyR1 siRNA and confirm that knocking down RyR1 concomitantly downregulates not only the DHPR but also the expression of other proteins involved in EC coupling. Unexpectedly, this was paralleled by the upregulation of inositol‐1,4,5‐triphosphate receptors; functionally however, upregulation of the latter Ca²⁺ channels did not compensate for the lack of RyR1‐mediated Ca²⁺ release. These results indicate that in some patients, RyR1 deficiency concomitantly alters the expression pattern of several proteins involved in calcium homeostasis and that this may influence the manifestation of these diseases.     

Detection of the aerolysin gene in Aeromonas hydrophila by the polymerase chain reaction.

Synthetic oligonucleotide primers were used in a polymerase chain reaction (PCR) technique to detect the gene for aerolysin in strains of Aeromonas hydrophila and to screen for identical genes in A. caviae, A. sobria, and A. veronii isolated from patients with diarrheal disease. Primers targeted a 209-bp fragment of the aer gene coding for the beta-hemolysin and detected template DNA only in the PCR using nucleic acid (NA) from hemolytic strains of A. hydrophila which were also cytotoxic to Vero and CHO cells and enterotoxic in suckling-mouse assays. PCR amplification of NA from hemolytic A. sobria or nonhemolytic A. hydrophila and A. caviae strains was consistently negative. Primer specificity was determined in the PCR by using NA extracted from 56 strains of bacteria, including hemolytic Escherichia coli and Listeria monocytogenes as well as several recognized enteric pathogens defined in terms of their toxigenicity. The detection limit for the aerolysin gene by PCR amplification was 1 ng of total NA. The PCR clearly identified aerolysin-producing strains of A. hydrophila and may have application as a species-specific virulence test because other hemolytic Aeromonas species tested were negative.     

Parents of adolescents with psychiatric disorders: insight into the disorder,self-stigma and parental stress

Background

Parents of adolescents with mental disorders experience stress partially due to the way they perceive and experience their offspring's disorder. The current study assessed the mediator role of self-stigma in the relationship between insight into the disorder and parental stress of parents of adolescents with mental disorders.

Method

A total of 37 parents of adolescents with psychiatric disorders were assessed for their level of insight, self-stigma and parental stress.

Results

The hypothesized mediation model was confirmed and is consistent with previous study on parents of adults with severe mental illness.

Discussion

The positive association between insight and parental stress is mediated by these parents' self-stigma, suggesting that insight increases the self-stigma, which in turn increases the parental stress. These results may have clinical implications with regard to the treatment of the family of adolescents with mental disorders.     

Amputation of finger by horse bite with complete avulsion of both flexor tendons

Amputation of fingers with tendon avulsion occurs through a traction injury, and most occur through a ring avulsion mechanism. Usually the flexor digitorum profundus is torn out with the amputated finger. Replantation usually is recommended only when the amputation is distal to the flexor digitorum superficialis insertion. Animal bites are relatively common, with a decreasing order of frequency of dogs, cats, and humans. Horse bites are relatively infrequent but are associated with crush injuries and tissue loss when they occur. This article describes a 23-year-old man with amputation of his middle finger at the level of the proximal phalanx after being bitten by a horse. The amputated stump was avulsed with the middle finger flexor digitorum profundus and flexor digitorum superficialis torn from the muscle-tendon junction from approximately the middle of the forearm. The patient had no other injuries, and he was able to move his other 4 fingers with only mild pain. As the amputated digit was not suitable for replantation, the wound was irrigated and debrided. The edges of the phalanx were trimmed, and the edges of the wound were sutured. Tetanus toxoid and rabies vaccine were administered, along with intravenous amoxicillin and clavulanic acid. The patient was discharged from the hospital 2 days later, with no sign of infection of the wound or compartment syndrome of the forearm. This case demonstrates the weakest point in the myotendinous junction and emphasizes the importance of a careful physical examination in patients with a traumatic amputation.     

Randomized controlled trial of calcaneal taping, sham taping, and plantar fascia stretching for the short-term management of plantar heel pain

STUDY DESIGN: Prospective, experimental, randomized, single-factor, pretest/posttest design. OBJECTIVES: To examine the effects of a calcaneal and Achilles-tendon-taping technique, utilizing only 4 pieces of tape and not involving the medial arch, on the symptoms of plantar heel pain. BACKGROUND: Plantar fasciitis is one of the most common causes of heel and foot pain. Physical therapists have applied many techniques in an attempt to relieve the symptoms of plantar heel pain, including various taping methods for which there is little existing evidence. METHODS AND MEASURES: Subjects (n=41) were randomly assigned into 4 groups: (1) stretching of the plantar fascia, (2) calcaneal taping, (3) control (no treatment), and (4) sham taping. A visual analog scale (VAS) for pain and a patient-specific functional scale (PSFS) for functional activities were measured pretreatment and after 1 week of treatment (posttreatment). Results: A significant difference was found posttreatment among the groups for the VAS (P < .001). Specifically, significant differences were found between stretching and calcaneal taping (mean + SD, 4.6 +/- 0.7 versus 2.7 +/- 1.8; P = .006), stretching and control (mean +/- SD, 4.6 +/- 0.7 versus 6.2 +/- 1.0; P = .026), calcaneal taping and control (mean +/- SD, 2.7 +/- 1.8 versus 6.2 +/- 1.0; P < .001), and calcaneal taping and sham taping (mean +/- SD, 2.7 +/- 1.8 versus 6.0 +/- 0.9; P < .001). No significant difference among groups was found for posttreatment PSFS (P = .078). Conclusions: Calcaneal taping was shown to be a more effective tool for the relief of plantar heel pain than stretching, sham taping, or no treatment.     

A pre-operative clinical scoring system to distinguish perforation risk with pediatric appendicitis

Importance

Appendicitis is a common, potentially serious pediatric disease. An important factor in determining management strategy [whether/when to perform appendectomy, duration of antibiotic therapy/hospitalization, etc.] and predicting outcome is distinguishing whether perforation is present.

A novel rapid and selective enzymatic debridement agent for burn wound management: A multi-center RCT

Objectives

Excisional debridement followed by autografting is the standard of care (SOC) for deep burns, but is associated with serious potential complications. Conservative, non-surgical and current enzymatic debridement methods are inefficiently slow. We determined whether a non-surgical option of rapid enzymatic debridement with the debriding enzyme NexoBrid™ (NXB) would reduce need for surgery while achieving similar esthetic and functional outcomes as SOC.

Methods

We conducted a multi-center, open-label, randomized, controlled clinical trial including patients aged 4-55 years with deep partial and full thickness burns covering 5-30% of their total body surface area (TBSA). Patients were randomly assigned to burn debridement with NXB (applied for 4 h) or SOC, which included surgical excisional or non-surgical debridement.

Results

NXB significantly reduced the time from injury to complete débridement (2.2 vs. 8.7 days, P < 0.0001), need for surgery (24.5% vs. 70.0%, P < 0.0001), the area of burns excised (13.1% vs. 56.7%, P < 0.0001) and the need for autografting (17.9% vs. 34.1%, P = 0.01). Scar quality and quality of life scores were similar in both study groups as were the rates of adverse events.

Conclusions

Enzymatic débridement with NXB resulted in reduced need for and extent of surgery compared with SOC while achieving comparable long-term results in patients with deep burns.

Trial registration

: Clinical Trials.gov NCT00324311.