A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT,the gene associated with Sanfilippo C mucopolysaccharidosis

Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors.     

Core components of communication of clinical reasoning: a qualitative study with experienced Australian physiotherapists

Communication is an important area in health professional education curricula, however it has been dealt with as discrete skills that can be learned and taught separate to the underlying thinking. Communication of clinical reasoning is a phenomenon that has largely been ignored in the literature. This research sought to examine how experienced physiotherapists communicate their clinical reasoning and to identify the core processes of this communication. A hermeneutic phenomenological research study was conducted using multiple methods of text construction including repeated semi-structured interviews, observation and written exercises. Hermeneutic analysis of texts involved iterative reading and interpretation of texts with the development of themes and sub-themes. Communication of clinical reasoning was perceived to be complex, dynamic and largely automatic. A key finding was that articulating reasoning (particularly during research) does not completely represent actual reasoning processes but represents a (re)construction of the more complex, rapid and multi-layered processes that operate in practice. These communications are constructed in ways that are perceived as being most relevant to the audience, context and purpose of the communication. Five core components of communicating clinical reasoning were identified: active listening, framing and presenting the message, matching the co-communicator, metacognitive aspects of communication and clinical reasoning abilities. We propose that communication of clinical reasoning is both an inherent part of reasoning as well as an essential and complementary skill based on the contextual demands of the task and situation. In this way clinical reasoning and its communication are intertwined, providing evidence for the argument that they should be learned (and explicitly taught) in synergy and in context.     

The effects of troglitazone,an insulin-sensitizing agent,on the endothelial function in early and late type 2 diabetes: a placebo-controlled randomized clinical trial

Activation of the peroxisome proliferator-activator receptor gamma (PPARgamma) improves insulin resistance and glycemic control in patients with diabetes. As PPARgamma is expressed in the endothelial cell, we have investigated the effect of troglitazone, a PPARgamma activator, on the endothelial function in people with type 2 diabetes in a 12-week, prospective, randomized, double-blinded clinical trial. We studied 87 type 2 diabetic patients who were divided into 3 groups. Group A consisted of 27 patients with recently diagnosed diabetes and no clinical manifestations of macrovascular disease; group B, 29 patients with long-term diabetes and no clinically evident macrovascular disease; and group C, 31 diabetic patients with documented macrovascular disease (cardiovascular, cerebrovascular, or peripheral vascular disease). High-resolution ultrasound images were used to measure the flow-mediated dilation (FMD, endothelium-dependent) and nitroglycerin-induced dilation (NID, endothelium-independent) in the brachial artery. Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine (Ach, endothelium-dependent) and 1% sodium nitroprusside (NaNP, endothelium-independent). The plasma concentrations of von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The FMD improved in the troglitazone-treated patients in group A (7.72 +/- 3.4 v 5.27 +/- 2.0, P <.05 [exit visit v baseline, percent of increase in brachial artery diameter, mean +/- SD]). The fasting insulin level also improved in this group (15.6 +/- 10 v 19.7 +/- 10, P <.05) and was strongly correlated to changes in FMD (r = -.73, P <.01). No changes were found in the FMD or the fasting insulin levels in the troglitazone-treated patients in groups B or C. The NID was not changed by troglitazone treatment in any of the 3 groups. Also, no differences were found in the microcirculation reactivity measurements or in the biochemical markers of endothelial dysfunction in all 3 groups. A small, but significant, improvement of the FMD was found in placebo-treated patients in group B, probably related to the low FMD levels at baseline in the patients (5.40 +/- 3.0 v 4.36 +/- 2.4, P <.05). We concluded that troglitazone treatment for 12 weeks improved endothelial function in the macrocirculation of patients with recently diagnosed type 2 diabetes and no clinical evidence of macrovascular disease. This improvement was strongly associated with the improvement of fasting plasma insulin concentrations.     

Sensory and inflammatory colonic changes induced by vincristine in distinct rat models of colitis

Preclinical and clinical studies show that gastrointestinal (GI) inflammation can evoke sensory changes occasionally far from the original inflammatory site. Animal models of colitis with either trinitrobenzenesulphonic acid (TNBS) or mustard oil (MO) produce distinct patterns of somatic and visceral sensory changes. We evaluated the effects of four doses of i.v. vincristine 150 μg kg^?1 (total of 600 μg kg^?1) treatment on the somatic (thermal nociceptive threshold) and colonic (morphological) changes induced by TNBS or MO in rats. TNBS and MO groups were further submitted to vincristine or saline pretreatments. TNBS induced somatic hypersensitivity, while MO induced somatic hyposensitivity (P < 0.05) when compared to the saline and ethanol control groups. Vincristine per se induced somatic hypersensitivity (P < 0.05). This effect was enhanced by TNBS and reversed by MO treatments. Although vincristine increased the colitis area (colonic weight length^?1 ratio) and the Morris' score in TNBS‐treated rats, it did not alter the colitis area and even lowered the Morris' score in MO‐treated rats. Compared to the saline (control) group, vincristine did not alter the colonic microscopic pattern. However, such lesions scores are higher (P < 0.05) in colitis groups induced by TNBS and MO, pretreated or not with vincristine. In conclusion, the somatic changes induced by different models of experimental colitis are diverse and modulated differently by vincristine.     

A randomized open-label trial of on-demand rabeprazole vs ranitidine for patients with non-erosive reflux disease

AIM: To compare the efficacy of the proton-pump inhibitor, rabeprazole, with that of the H₂-receptor antagonist, ranitidine, as on-demand therapy for relieving symptoms associated with non-erosive reflux disease (NERD).METHODS: This is a single center, prospective, randomized, open-label trial of on-demand therapy with rabeprazole (group A) vs ranitidine (group B) for 4 wk. Eighty-three patients who presented to the American University of Beirut Medical Center with persistent gastroesophageal reflux disease (GERD) symptoms and a normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A (n = 44) were allowed a maximum rabeprazole dose of 20 mg twice daily, while those in group B (n = 39) were allowed a maximum ranitidine dose of 300 mg twice daily. Efficacy was assessed by patient evaluation of global symptom relief, scores of the SF-36 quality of life (QoL) questionnaires, total number of pills used, and number of medication-free days.RESULTS: Among the 83 patients who were enrolled in the study, 76 patients (40 in the rabeprazole group and 36 in the ranitidine group) completed the 4-wk trial. Baseline characteristics were comparable between both groups. After 4 wk, there was no significant difference in the subjective global symptom relief between the rabeprazole and the ranitidine groups (71.4% vs 65.4%, respectively; P = 0.9). There were no statistically significant differences between mean cumulative scores of the SF-36 QoL questionnaire for the two study groups (rabeprazole 22.40 ± 27.53 vs ranitidine 17.28 ± 37.06; P = 0.582). There was no significant difference in the mean number of pills used (rabeprazole 35.70 ± 29.75 vs ranitidine 32.86 ± 26.98; P = 0.66). There was also no statistically significant difference in the mean number of medication-free days between both groups.CONCLUSION: Rabeprazole has a comparable efficacy compared to ranitidine when given on-demand for the treatment of NERD. Both medications were associated with improved quality of life.     

Gender Differences in the Heritability of Musculoskeletal and Body Composition Parameters in Mother-Daughter and Mother-Son Pairs

Bone mass and body composition traits are genetically programmed, but the timing and gender and site specificities of their heritability are unclear. Mother-child correlations of bone mineral density (BMD) and bone mineral content, lean mass, and fat mass were studied in 169 premenopausal mothers and their 239 children. Heritability estimates of lean mass, fat mass, BMD, and area were derived for each gender and pubertal stage. There were significant correlations for most densitometry-derived variables at the spine, hip, femoral neck (FN), and total body (r = 0.192–0.388) in mother-postmenarcheal daughter pairs, for bone areas at all sites in early puberty (r = 0.229–0.508) and for volumetric-derived density at FN and spine (r = 0.238–0.368) in mother-son pairs. Fat mass correlations were significant in both genders after puberty (r = 0.299–0.324) and lean mass in postmenarcheal girls only (r = 0.299). Heritability estimates varied between 21% and 37% for mother-daughter and 18% and 35% for mother-son pairs for density-derived variables and between 26% and 40% for body composition variables. Maternal inheritance of bone traits is expressed in early-pubertal boys for several skeletal site traits but consistently involves most site traits in girls and boys by late puberty. Body composition inheritance is more variable.     

A comparison between screw- and cement-retained implant prostheses. A literature review

Implant-supported restorations can be secured to implants with screws (screw-retained), or they can be cemented to abutments which are attached to implants with screws (cement-retained). This literature review discusses the advantages and disadvantages of each method of retention from different aspects. These aspects include: ease of fabrication and cost, esthetics, access, occlusion, retention, incidence of loss of retention, retrievability, clinical prosthesis fit, restriction of implant position, effect on peri-implant tissue health, provisionalization, immediate loading, impression procedures, porcelain fracture, and clinical performance. Peer-reviewed literature published in the English language between 1955 and 2010 was reviewed using PubMed and hand searches. Since the choice of using either method of retention is still controversial, this review article offers some clinical situations that prefer one method of retention over the other. The review demonstrated that each method of retention has certain advantages and disadvantages; however, there are some clinical situations in which it is better to select one method of retention rather than the other.