Improved Real-World Glycemic Control With Continuous Glucose Monitoring System Predictive Alerts

Background:Most standalone real-time continuous glucose monitoring (RT-CGM) systems provide predictive low and high sensor glucose (SG) threshold alerts. The durations and risk of low and high SG excursions following Guardian™ Connect CGM system predictive threshold alerts were evaluated.Methods:Continuous glucose monitoring system data uploaded between January 2, 2017 and May 22, 2018 by 3133 individuals using multiple daily injections (MDIs) or continuous subcutaneous insulin infusion (CSII) therapy were deidentified and retrospectively analyzed. Glucose excursions were defined as SG values that went beyond a preset low or high SG threshold for ≥15 minutes. For a control group, thresholds were based on the median of the low SG threshold limit (70 mg/dL) and the high SG threshold limit (210 mg/dL) preset by all system users. During periods when alerts were not enabled, timestamps were identified when a predictive alert would have been triggered. The time before low horizon was 17.5 minutes and the time before high horizon was 15 minutes, of all users who enabled alerts. Excursions occurring after a low SG or high SG predictive alert were segmented into prevented, ≤20, 20-60, and >60 minutes.Results:Excursions were prevented after 59% and 39% of low and high SG predictive alerts, respectively. The risk of a low or high excursion occurring was 1.9 (P < 0.001, 95% CI, 1.88-1.93) and 3.3 (P < 0.001, 95% CI, 3.20-3.30) times greater, respectively, when alerts were not enabled.Conclusions:The predictive alerts of the RT-CGM system under study can help individuals living with diabetes prevent some real-world low and high SG excursions. This can be especially important for those unable to reach or maintain glycemic control with basic RT-CGM or CSII therapy.     

Quality of life and neurobehavioral changes in survivors of malignant middle cerebral artery infarction

Malignant middle cerebral artery (MMCA) infarction is associated with a mortality rate of 80% under conservative treatment. Decompressive hemicraniectomy (DH) reduces mortality and improves the functional outcome of surviving patients. The purpose of this study was to examine quality of life (QoL) and neurobehavioral deficits in patients with space-occupying infarctions of the right- or left-sided hemisphere at 6 months after stroke. The Sickness Impact Profile (SIP) was used to assess QoL in 19 out of 29 consecutive patients that underwent DH after a malignant MCA infarction (14 on the right and 5 on the left hemisphere). Behavioral changes were evaluated with the Frontal Behavioral Inventory and the Beck Depression Inventory. Patients and relatives were also asked if, knowing the present outcome, they would agree again, in retrospect, to a DH. Barthel Index >60 was seen in 37% of our patients. Functional outcome was related to age. We found a higher reduction in the SIP’s physical domain than in the psychosocial domain. Depressive symptoms were present in 50% of the patients. We didn’t find significant differences in QoL or functional outcome between patients with right or left-sided infarctions. The most frequent neurobehavioral symptoms were decreased speech output, apathy, reduced spontaneity and irritability. Most patients and their relatives would again give consent to hemicraniectomy. The results show that younger patients had a significantly better outcome. QoL seems to be acceptable in both left- and right-sided infarctions, and retrospective agreement to hemicraniectomy is high in both patients and their relatives.     

Methamphetamine-induced neurotoxicity: the road to Parkinson’s disease

Studies have implicated methamphetamine exposure as a contributor to the development of Parkinson’s disease. There is a significant degree of striatal dopamine depletion produced by methamphetamine, which makes the toxin useful in the creation of an animal model of Parkinson’s disease. Parkinson’s disease is a progressive neurodegenerative disorder associated with selective degeneration of nigrostriatal dopaminergic neurons. The immediate need is to understand the substances that increase the risk for this debilitating disorder as well as these substances’ neurodegenerative mechanisms. Currently, various approaches are being taken to develop a novel and cost-effective anti-Parkinson’s drug with minimal adverse effects and the added benefit of a neuroprotective effect to facilitate and improve the care of patients with Parkinson’s disease. A methamphetamine-treated animal model for Parkinson’s disease can help to further the understanding of the neurodegenerative processes that target the nigrostriatal system. Studies on widely used drugs of abuse, which are also dopaminergic toxicants, may aid in understanding the etiology, pathophysiology and progression of the disease process and increase awareness of the risks involved in such drug abuse. In addition, this review evaluates the possible neuroprotective mechanisms of certain drugs against methamphetamine-induced toxicity.     

A lateral cephalometric analysis of nasal morphology following Le Fort I osteotomy applying photometric analysis techniques

Fifty patients who had undergone Le Fort I maxillary osteotomies were studied. Cephalograms were available preoperatively and at least 6 months postoperatively. Soft-tissue analysis of the nasal profile was done employing three angles commonly used in the photometric analysis performed for rhinoplasty: nasal tip projection angle, columellar angle, and supratip break angle. Maxillary movement was assessed in two ways: 1) horizontal and vertical component vectors of A-point movement were calculated, and 2) maxillary rotation, defined as the change in the angle of a line drawn from the anterior nasal spine to the posterior nasal spine relative to the anterior cranial base, was calculated. The component vectors of A-point movement and maxillary rotation were then used as predictor variables for change in the soft-tissue angles in a multiple-regression analysis. A weak correlation was found between A-point movement in both the horizontal and vertical dimensions and the nasal tip projection angle. When A-point was moved in an anterior and superior direction, the nasal tip rotated up. The converse was true with movement in the posterior and inferior direction. Only A-point movement in the horizontal dimension had a significant relationship with columellar angle. When A-point was moved in an anterior direction, columellar angle increased. This study shows that prediction of the soft-tissue profile of the nose following maxillary surgery is difficult.     

Cytokine Production in the Serum and Spleen of Mice from Day 6 to 14 of Gestation: Cytokines/Placenta/ Spleen/Serum

Pregnancy, like most biologic phenomena, involves the action of cytokines. These proteins have a short half-life and are believed to exert their effect close to their site of production, where diagnostic tests cannot be easily performed. Here we show that the cytokine content in the maternal serum reflects cytokine production and secretion from maternal spleen cells, which also correlates with production from decidual cells. We show that GM-CSF, IL- 3, and IL-10 are present in the serum at specific time intervals during the first half of murine pregnancy, which correlates with their production from maternal spleen cells. Purified GM-CSF and IL-3 from spleen-cell-culture supernatants are biologically active molecules, able to stimulate placental-cell proliferation. Furthermore, TNF-0, which has been identified in many cases of fetal rejection as well as in labor, is shown to be naturally produced during the second half of pregnancy. Additionally, within the limits of the sensitivity of the technique we have used, the detection of IL-4 and the absence of detectable levels of IL- 2 in the maternal serum strongly comforts the hypothesis that pregnancy is a Th2-dependent phenomenon. The results presented in this paper show that the cytokine profile during pregnancy can be monitored by simple blood tests, which may be of relevance both in the followup of a physiological human pregnancy and to the diagnosis of recurrent abortions due to cytokine imbalance.     

Maximal Concanavalin A-Specific Agglutinability Without Loss of Density-Dependent Growth Control

Density-inhibited 3T3 mouse fibroblasts were treated for 10 min with nine concentrations of Pronase ranging from 0.25 to 40 mug/ml. Concanavalin A-specific agglutinability increased from control values of about 25% to plateau values of about 80%. None of these Pronase concentrations brought about an increase in cell number within 84 hr. Pronase-treated cells remained responsive to growth stimulation by serum and cortisol. Therefore, the protease-mediated surface change measured by increased concanavalin A-specific agglutinability is not an event sufficient by itself to bring about cell division.     

Upregulation of the stress-associated gene p8 in mouse models of demyelination and in multiple sclerosis tissues

Cuprizone-induced demyelination is a mouse model of multiple sclerosis (MS) as cuprizone-fed mice exhibit neuroinflammation and demyelination in the brain. Upon removal of cuprizone from the diet, inflammation is resolved and reparative remyelination occurs. In an Affymetrix GeneChip analysis, the stress-associated gene p8 was strongly upregulated (>10x) during cuprizone-induced demyelination but not remyelination. We verified this upregulation (>15x) of p8 in the CNS during demyelination by real-time polymerase chain reaction (PCR). This upregulation is brain-specific, as p8 is not elevated in the liver, lung, kidney, spleen, and heart of cuprizone-treated mice. We also localized the cellular source of p8 during cuprizone treatment, and further found elevated expression during embryogenesis but not in normal adult brain. Compared with wild-type controls, the death of oligodendrocytes in p8-/- mice is delayed, as is microglial recruitment to areas of demyelination. The corpus callosum of p8-/- mice demyelinates at a slower rate than wild-type mice, suggesting that p8 exacerbates CNS inflammation and demyelination. Enhanced expression of p8 is also observed in the spinal cords of mice with acute experimental autoimmune encephalomyelitis (EAE) induced by PLP139-151 peptide (10x). Increased expression is detected during disease onset and expression wanes during the remission phase. Finally, p8 is found upregulated (8x) in post-mortem tissue from MS patients and is higher in the plaque tissue compared with adjacent normal-appearing white and gray matter. Thus, p8 is an excellent candidate as a novel biomarker of demyelination.     

A retrospective study of relapse in rigidly fixated sagittal split osteotomies: contributing factors

Fifty-one patients who underwent mandibular advancements with or without genioplasties were rigidly fixated with three, 2-mm bicortical screws per side. Radiographs were digitized preoperatively, immediately postoperatively, at 6 weeks, at 6 months, and at a subsequent long-term follow-up period. Location of the cephalometric landmarks, referenced to a vertical reference line (in millimeters), was used as the dependent variable. An overall inspection of the data shows that rigidly fixated mandibular advancements were very stable. The average case showed further advancement of pogonion from 6 weeks to the long-term follow-up period. However, relapse was noted in several cases. Factors that could be used as predictors of relapse were examined. Results indicated that magnitude of advancement was the only factor that successfully predicted relapse, accounting for 37.9% of the variance in the sample. Anatomic changes found to accompany such advancement are as follows: (1) when pogonion comes forward, anterior facial height and mandibular plane decrease while the proximal segment rotates forward, and (2) the maxillary central incisors flare and the mandibular incisors upright during this time period. A small degree of relapse as assessed at pogonion occurred during the first 6 weeks, followed by an advancement from 6 weeks to the longest time interval after the surgical procedure. However, these directional movements were not statistically significant.