Correction to: Effect of Opioid Use on Immune Activation and HIV Persistence on ART

Journal of Neuroimmune Pharmacology - The original version of this article unfortunately contained mistakes.     

When Genetic Load Does Not Correlate with Phenotypic Spectrum: Lessons from the GnRH Receptor (GNRHR)

Context: A broad spectrum of GnRH-deficient phenotypes has been identified in individuals with both mono- and biallelic GNRHR mutations. Objective: The objective of the study was to determine the correlation between the severity of the reproductive phenotype(s) and the number and functional severity of rare sequence variants in GNRHR. Subjects: Eight hundred sixty-three probands with different forms of GnRH deficiency, 46 family members and 422 controls were screened for GNRHR mutations. The 70 subjects (32 patients and 38 family members) harboring mutations were divided into four groups (G1-G4) based on the functional severity of the mutations (complete or partial loss of function) and the number of affected alleles (monoallelic or biallelic) with mutations, and these classes were mapped on their clinical phenotypes. Results: The prevalence of heterozygous rare sequence variants in GNRHR was significantly higher in probands vs. controls (P < 0.01). Among the G1-G3 groups (homozygous subjects with successively decreasing severity and number of mutations), the hypogonadotropic phenotype related to their genetic load. In contrast, subjects in G4, with only monoallelic mutations, demonstrated a greater diversity of clinical phenotypes. Conclusions: In patients with GnRH deficiency and biallelic mutations in GNRHR, genetic burden defined by severity and dose is associated with clinical phenotype. In contrast, for patients with monoallelic GNRHR mutations this correlation does not hold. Taken together, these data indicate that as-yet-unidentified genetic and/or environmental factors may combine with singly mutated GNRHR alleles to produce reproductive phenotypes.     

Surgical treatment of bisphosphonate-associated osteonecrosis of the jaw: Technical report and follow up of 21 patients

IntroductionBisphosphonates are used to reduce skeletal related events in patients with bone consuming diseases such as osteoporosis and bone metastases. However recently there has been an increased awareness of bisphosphonate-associated necrosis of the jaws (BP-ONJ). Many authors propose conservative management in these cases but invariably the problem is not treated successfully allowing the bone defect to worsen. Recently there has been a move to treat this problem surgically. The aim of this retrospective study was to provide a surgical solution for patients suffering from BP-ONJ.Materials and methodsAll patients presenting with BP-ONJ were treated with bone debridement of the affected area and multilayer wound closure. The considered variables were: gender, age, underlying diagnosis, type of bisphosphonate (BP) used, duration of bisphosphonate use, route of administration, location of the osteonecrosis, clinical symptoms, association with dental treatment and surgical outcome.ResultsNineteen cases of a total of 21 demonstrated no recurrence of osteonecrosis during follow up (Mean 16 months – Range 12–24 months). One patient with a bilateral defect showed a dehiscence on one side and a small fistula on the contralateral side 6 weeks post-operatively and required revision surgery. Another patient developed a fistula after 4 weeks that was treated successfully with antibiotics and curettage. No patients had evidence of exposed bone, bland mucosa nor pain at the surgical site.ConclusionThe technique described can be recommended for patients with BP-ONJ if a conservative treatment fails.     

Exercise during energy restriction mitigates bone loss but not alterations in estrogen status or metabolic hormones

Summary

Energy restriction causes bone loss, increasing stress fracture risk. The impact of exercise during energy restriction on bone and endocrine factors is examined. Exercise with energy restriction did not influence endocrine factors, but did mitigate some bone loss seen with energy restriction in sedentary rats.

Introduction

Chronic dietary energy restriction (ER) leads to bone loss and increased fracture risk. Strictly controlled trials of long-term ER with and without vigorous exercise are required to determine whether exercise loading can counterbalance ER-induced bone loss. The aim of this current project is to elucidate the impact of exercise and ER on bone mass, estrogen status, and metabolic hormones.

Methods

Twenty-four virgin female Sprague-Dawley rats (n?=?8/group) were divided into three groups—ad libitum fed?+?exercise (Adlib?+?EX), 40 % energy restricted?+?exercise (ER?+?EX), and 40 % energy restricted?+?sedentary (ER?+?SED). Energy availability between ER groups was equal. Treadmill running was performed 4 days/week at 70 % VO_2max for 12 weeks.

Results

Fat and lean mass and areal bone mineral density (aBMD) were lower after 12 weeks (p?<?0.05) for ER?+?EX vs Adlib?+?EX, but ER?+?EX aBMD was higher than ER?+?SED (p?<?0.0001). Serum leptin and a urinary estrogen metabolite, estrone-1-glucuronide (E1G), were lower at week 12 (p?=?0.0002) with ER, with no impact of exercise. Serum insulin-like growth factor I (IGF-I) declined (p?=?0.02) from baseline to week 12 in both ER groups. ER?+?EX exhibited higher cortical volumetric bone mineral density (vBMD) at the midshaft tibia (p?=?0.006) vs ER?+?SED.

Conclusion

Exercise during ER mitigated some, but not all, of the bone loss observed in sedentary ER rats, but had little impact on changes in urinary E1G and serum IGF-I and leptin. These data highlight the importance of both adequate energy intake and the mechanical loading of exercise in maintaining bone mass.