ObjectiveCompared with hemoglobin A1c (HbA1c), continuous glucose monitoring (CGM) may better capture risk of diabetes complications in patients with chronic kidney disease (CKD), including diabetic peripheral neuropathy (DPN). We hypothesized that glucose time in range (TIR), measured by CGM, is associated with DPN symptoms among participants with type 2 diabetes mellitus (type 2 DM) and moderate-to-severe CKD.Research design and methodsWe enrolled 105 people with type 2 DM treated with insulin or sulfonylurea, 81 participants with CKD (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2) and 24 matched control participants with eGFR ≥60 mL/min/1.73 m2. Each participant wore a CGM for two 6-day periods. Calculated glycemic measures included TIR (glucose 70–180 mg/dL) and glucose management indicator (GMI). DPN symptoms were assessed using the Michigan Neuropathy Screening Instrument (MNSI) questionnaire, with a positive MNSI score defined as ≥2 symptoms.ResultsParticipants with CKD had a mean age of 68 years, diabetes duration 20 years, eGFR 38 mL/min/1.73 m2 and HbA1c 7.8%, 61 mmol/mol. Sixty-two participants reported ≥2 DPN symptoms, 51 (63%) with CKD and 11 (46%) controls. Less TIR and higher GMI were associated with higher risk of MNSI questionnaire score ≥2 (OR 1.25 (95% CI 1.02 to 1.52) per 10% lower TIR, and OR 1.79 (95% CI 1.05 to 3.04) per 1% higher GMI, adjusting for age, gender and race). Similar results were observed when analyses were restricted to participants with CKD. In contrast, there was no significant association of HbA1c with DPN symptoms.ConclusionsSymptoms of DPN were common among participants with long-standing type 2 DM and CKD. Lower TIR and higher GMI were associated with DPN symptoms.
Objective To systematically review the literature on anti-inflammatory medications for treating pediatric obstructive sleep apnea and perform meta-analysis of the available data. Data Sources PubMed/MEDLINE and 4 additional databases. Review Methods Three authors independently and systematically searched through June 28, 2018, for studies that assessed anti-inflammatory therapy for treatment of pediatric obstructive sleep apnea (OSA). Data were compiled and analyzed using Review Manager 5.3 (Nordic Cochrane Centre). Results After screening 135 studies, 32 were selected for review with 6 meeting inclusion criteria. In total, 668 patients aged 2 to 5 years met inclusion criteria for meta-analysis. Of these, 5 studies (166 children) that evaluated montelukast alone as treatment for pediatric OSA found a 55% improvement in the apnea-hypopnea index (AHI) (mean [SD] 6.2 [3.1] events/h pretreatment and 2.8 [2.7] events/h posttreatment; mean difference [MD] of −2.7 events/h; 95% confidence interval [CI], –5.6 to 0.3) with improvement in lowest oxygen saturation (LSAT) from 89.5 (6.9) to 92.1 (3.6) (MD, 2.2; 95% CI, 0.5-4.0). Two studies (502 children) observing the effects of montelukast with intranasal corticosteroids on pediatric OSA found a 70% improvement in AHI (4.7 [2.1] events/h pretreatment and 1.4 [1.0] events/h posttreatment; MD of −4.2 events/h; 95% CI, –6.3 to −2.0), with an improvement in LSAT from 87.8 (3.1) to 92.6 (2.2) (MD, 4.8; 95% CI, 4.5-5.1). Conclusions Treatment with montelukast and intranasal steroids or montelukast alone is potentially beneficial for short-term management of mild pediatric OSA.
Niemann-Pick C disease (NPC) is an irreversible neurodegenerative disorder without current treatment. It is thought to result from deficient intracellular cholesterol and/or ganglioside trafficking. We have investigated the effects of allopregnanolone treatments on survival, weight loss, motor function, magnetic resonance imaging (MRI), and neuropathology in the mouse model of NPC (Npc1(-/-) mice). We confirmed previous results showing that a single injection of 250 microg of allopregnanolone on postnatal day 7 significantly extended the life span of Npc1(-/-) mice. This caused a marked difference in the weight curves of the treated mice but no statistical difference in the Rota-Rod performance. T2-weighted MRI and diffusion tensor imaging (DTI) of treated mice showed values of signal intensity and fractional anisotropy closer to those of wild-type mice than those of untreated Npc1(-/-) mice. Neuropathology showed that day-7 treatment markedly suppressed astrocyte reaction and significantly reduced microglial activation. Furthermore, the steroid treatment also increased myelination in brains of Npc1(-/-) mice. Similar effects of allopregnanolone treatment were observed in Npc1(-/-), mdr1a(-/-) double-mutant mice, which have a deficient blood-brain barrier, resulting in increased steroid uptake. The effects on survival and weight loss of a single injection on day 7 followed by injections every 2 weeks were also evaluated in Npc1(-/-) mice, and the beneficial effects were found to be greater than with the single injection at day 7. We conclude that allopregnanolone treatment significantly ameliorates several symptoms of NPC in Npc1(-/-) mice, presumably by effects on myelination or neuronal connectivity.
Objective Lack of ergonomic training and poor ergonomic habits during the operation leads to musculoskeletal pain and affects the surgeon’s life outside of work. The objective of the study was to evaluate the severity of ergonomic hazards in the surgical profession across a wide range of surgical subspecialties. We conducted intraoperative observations using Rapid Entire Body Assessment (REBA) score system to identify ergonomic hazards. Additionally, each of the ten surgical subspecialty departments were sent an optional 14 question survey which evaluated ergonomic practice, environmental infrastructure, and prior ergonomic training or education. A total of 91 surgeons received intraoperative observation and were evaluated on the REBA scale with a minimum score of 0 (low ergonomic risk <3) and a maximum score of 10 (high ergonomic risk 8–10). And a total of 389 surgeons received the survey and 167 (43%) surgeons responded. Of the respondents, 69.7% reported suffering from musculoskeletal pain. Furthermore, 54.9% of the surgeons reported suffering from the highest level of pain when standing during surgery, while only 14.4% experienced pain when sitting. Importantly, 47.7% stated the pain impacted their work, while 59.5% reported pain affecting quality of life outside of work. Only 23.8% of surgeons had any prior ergonomic education. Both our subjective and objective data suggest that pain and disability induced by poor ergonomics are widespread among the surgical community and confirm that surgeons rarely receive ergonomic training. Intraoperative observational findings identified that the majority of observed surgeons displayed poor posture, particularly a poor cervical angle and use of ergonomic setups, both of which increase ergonomic risk hazards. This data supports the need for a comprehensive ergonomic interventional program for the surgical team and offers potential targets for future intervention.
Although the primary purpose of using digital photography in dentistry is for recording various aspects of clinical information in the oral cavity, other benefi ts also accrue. Detailed here are the uses of digital images for dento-legal documentation, education, communication with patients, dental team members and colleagues and for portfolios, and marketing. These uses enhance the status of a dental practice and improve delivery of care to patients.
Vestibular schwannomas (VSs) arise from Schwann cells (SCs) and result from the loss of function of merlin, the protein product of the NF2 tumor suppressor gene. In contrast to non-neoplastic SCs, VS cells survive long-term in the absence of axons. We find that p75NTR is over-expressed in VSs compared with normal nerves, both at the transcript and protein level, similar to the response of non-neoplastic SCs following axotomy. Despite elevated p75NTR expression, VS cells are resistant to apoptosis due to treatment with pro-NGF, a high affinity ligand for p75NTR. Furthermore, treatment with proNGF protects VS cells from apoptosis due to c-Jun N-terminal kinase (JNK) inhibition indicating that p75NTR promotes VS cell survival. Treatment of VS cells with proNGF activated NF-κB while inhibition of JNK with SP600125 or siRNA-mediated knockdown reduced NF-κB activity. Significantly, proNGF also activated NF-κB in cultures treated with JNK inhibitors. Thus, JNK activity appears to be required for basal levels of NF-κB activity, but not for proNGF-induced NF-κB activity. To confirm that the increase in NF-κB activity contributes to the prosurvival effect of proNGF, we infected VS cultures with Ad.IκB.SerS32/36A virus, which inhibits NF-κB activation. Compared to control virus, Ad.IκB.SerS32/36A significantly increased apoptosis including in VS cells treated with proNGF. Thus, in contrast to non-neoplastic SCs, p75NTR signaling provides a prosurvival response in VS cells by activating NF-κB independent of JNK. Such differences may contribute to the ability of VS cells to survive long-term in the absence of axons.
The ACGME News and Views section of JGME includes data reports, updates, and perspectives from the ACGME and its review committees. The decision to publish the article is made by the ACGME.
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