Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial.

Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 >500 cells/µL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomized trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 <350 cells/µL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80% non-white, 26% women, median CD4 count 642 cells/µL). ART (most commonly including tenofovir and efavirenz) was used for 95% and 18% of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (-2.5% versus -1.0%; difference -1.5%, 95% confidence interval [CI] -2.2 to -0.8, p < 0.001) and spine (-1.9% versus -0.4%; difference -1.6%, 95% CI -2.2 to -1.0, p < 0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, whereas hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related, or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis because of the reduced risk of serious clinical outcomes. Better understanding of the longer-term consequences of the observed reductions in BMD is needed. CLINICAL TRIALS REGISTRATION: NCT00867048. © 2017 American Society for Bone and Mineral Research.

Nanodiamonds of Laser Synthesis for Biomedical Applications.

In recent decade detonation nanodiamonds (DND), discovered 50 years ago and used in diverse technological processes, have been actively applied in biomedical research as a drug and gene delivery carrier, a contrast agent for bio-imaging and diagnostics and an adsorbent for protein separation and purification. In this work we report about nanodiamonds of high purity produced by laser assisted technique, compare them with DND and consider the prospect and advantages of their use in the said applications.

Special delivery: targeted therapy with small RNAs.

Harnessing RNA interference using small RNA-based drugs has great potential to develop drugs designed to knock down expression of any disease-causing gene, thereby greatly expanding the universe of possible drug targets. However, delivering small RNAs into specific tissues and cells is still a hurdle. Here, we review recent progress in overcoming systemic, local and cellular barriers to RNA drug delivery, focusing on strategies for targeted uptake.

A giant syphilitic aneurysm in a young human immunodeficiency virus sero-positive individual.

A 35-year-old, human immunodeficiency virus sero-positive male presented with huge mediastinal mass for evaluation. After contrast enhanced computed tomography (CECT) angiogram, aneurysm of arch of aorta was diagnosed. The patient also proved to be co-infected with syphilis, which is the aetiological cause of aneurysm in this case. The present report highlights the need to suspect, diagnose and treat dual infections in individuals with high risk behaviour.

Physicochemical evaluation of a stability-driven approach to drug entrapment in regular and in surface-modified liposomes.

The traditional mode of encapsulating drugs in liposomes poses risks to drug stability, especially when recognition agents are attached to the liposomal surface to obtain targeted liposomes. To reduce such risks, we devised a simple, novel method to entrap drugs in liposomes, consisting of (i) preparation and lyophilization of drug-free regular and surface-modified liposomes and (ii) drug encapsulation in the course of liposome reconstitution through rehydration in an aqueous solution of the drug. In this paper, we report physicochemical studies in which we compared regular and surface-modified liposomes made by this novel approach (denoted N-liposomes) to respective liposomes made by the traditional mode (denoted T-liposomes). The studies were performed with fluorescein, sucrose, histidine, mitomycin C (MMC), and chloramphenicol (CAM) encapsulated (each) in regular and in bioadhesive liposomes, the latter having hyaluronic acid as the surface-bound ligand. Our major findings are as follows: (1) The drug-specific encapsulation efficiencies spanning the range of 10-90% were, excepting sucrose, either similar in the N- and T-liposomes or better in the N- than in the T-liposomes, for both regular and bioadhesive liposomes. (2) For all liposome types and methods of preparation, fluorescein, histidine, and MMC did not adsorb to the liposomal surface. Sucrose and MMC did adsorb to the liposomal surface irrespective of the liposome preparation mode, sucrose favoring bioadhesive over regular liposomes and MMC having the opposite trend. (3) For both regular and bioadhesive liposomes, the mechanism of drug efflux from the N-liposomes was found to be governed by a single rate constant, as previously found for the T-liposomes. The magnitudes obtained, ranging from 3.5(+/-0.2) x 10(-3) to 400(+/-17) x 10(-3) h(-1), were always drug specific and occasionally also liposome type (i.e., regular or bioadhesive) specific. For MMC and CAM, the novel approach rendered liposomes with improved sustained release. The results reported here attest, overall, to the potential of this novel approach, meriting further investigations. Studies currently underway with MMC indicate N-liposomes also have functional advantages.

[Prenatal diagnosis of the pentalogy of Cantrell combined with exencephaly and amniotic band syndrome]. / Pränatale Diagnose einer Cantrellschen Pentalogie kombiniert mit Exenzephalie und Amnionbridensyndrom.

A case of pentalogy of Cantrell associated with exencephaly and amniotic band syndrome, detected by ultrasound and then confirmed by pathological findings, is reported. Both conditions are very rare, usually occurring as a single anomaly; their association has not been reported in the literature. One should consider in differential diagnosis of pentalogy of Cantrell the omphalocele and the body stalk syndrome, and of exencephaly the osteogenesis imperfecta together with disorders of mineralisation. A viral infection could play a part in the aetiology of this condition.

[Transitory osteoporosis in pregnancy; diagnosis with MRI. Case report]. / Transitorische Osteoporose in der Schwangerschaft; Diagnose mittels MRI. Fallbericht.

A case of transitory osteoporosis of the hips in pregnancy is reported. Through knowledge of the typical course of the disease and exact diagnosis with MRI, expensive therapy can be avoided. Suspicion of a transitory osteoporosis in pregnancy is a clear indication for performing an MRI.

[Combined surgical-antibiotic therapy of actinomycosis of the adnexa]. / Kombiniert operativ-antibiotische Therapie der Adnexactinomykose.

The majority of patients presenting with tubo-ovarian abscess caused by abdominopelvic actinomycosis are women using an IUD. Since the course of this disease is afebrile, and the diagnosis often established relatively late, it typically simulates a malignant tumour of the lower abdomen. Except for leukocytosis and an increased blood sedimentation rate, laboratory findings are within the normal range. The infection infiltrates neighboring structures, and hence a secondary involvement of the intestine is common. Two cases are presented, successfully treated by a combined operative-antibiotic approach.

Effect of skip-a-day feed restriction on the jejunal mucosa of broiler breeder pullets.

Jejunal tissue was taken from 18-week-old broiler breeder pullets previously reared on a daily or skip-a-day feed restriction system. Light and scanning electron microscopy revealed no changes in mucosal appearance or structure related to feeding system. Comparable duodenal samples all revealed extensive desquamated epithelial damage possibly related to postmortem change.