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Bipolar Disorder (BD) is a severe and chronic disorder characterized by recurrent episodes of depression, mania, and/or hypomania. Most BD patients initially present with depressive symptoms, resulting in a delayed diagnosis of BD and poor clinical outcomes. This study leverages electronic health record (EHR) data from the Clínica San Juan de Dios Manizales in Colombia to identify features predictive of the transition from Major Depressive Disorder (MDD) to BD. Analyzing EHR data from 13,607 patients diagnosed with MDD over 15 years, we identified 1,610 cases of conversion to BD. Using a multivariate Cox regression model, we identified severity of the initial MDD episode, the presence of psychosis and hospitalization at first episode, family history of mood or psychotic disorders, female gender to be predictive of the conversion to BD. Additionally, we observed associations with medication classes (prescriptions of mood stabilizers, antipsychotics, and antidepressants) and clinical features (delusions, suicide attempt, suicidal ideation, use of marijuana and alcohol use/abuse) derived from natural language processing (NLP) of clinical notes. Together, these risk factors predicted BD conversion within five years of the initial MDD diagnosis, with a recall of 72% and a precision of 38%. Our study confirms many previously identified risk factors identified through registry-based studies (such as female gender and psychotic depression at the index MDD episode), and identifies novel ones (specifically, suicidal ideation and suicide attempt extracted from clinical notes). These results simultaneously demonstrate the validity of using EHR data for predicting BD conversion as well as underscore its potential for the identification of novel risk factors and improving early diagnosis.

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F1-protein fraction (F1) is a natural bioactive compound extracted from the rubber tree, Hevea brasiliensis, and has been recently studied for its therapeutic potential in wound healing. In this study, we investigated the concentration-dependent effects of F1 (0.01%, 0.025%, 0.05%, and 0.1%) incorporated into deproteinized bovine bone (DBB) and porous biphasic calcium phosphate (pBCP), on the repair of rat calvarial critical-size bone defects (CSBD). The defects were analyzed by 3D-microtomography and 2D-histomorphometry at 12 weeks postsurgery. The binding efficiency of F1 to pBCP (96.3 ± 1.4%) was higher than that to DBB (67.7 ± 3.3%). In vivo analysis showed a higher bone volume (BV) gain in all defects treated with DBB (except in 0.1% of F1) and pBCP (except in 0.05% and 0.1% of F1) compared to the CSBD without treatment/control group (9.96 ± 2.8 mm3 ). DBB plus 0.025% F1 promoted the highest BV gain (29.7 ± 2.2 mm3 , p < .0001) compared to DBB without F1 and DBB plus 0.01% and 0.1% of F1. In the pBCP group, incorporation of F1 did not promote bone gain when compared to pBCP without F1 (15.9 ± 4.2 mm3 , p > .05). Additionally, a small BV occurred in defects treated with pBCP plus 0.1% F1 (10.4 ± 1.4 mm3, p < .05). In conclusion, F1 showed a higher bone formation potential in combination with DBB than with pBCP, in a concentration-dependent manner. Incorporation of 0.25% F1 into DBB showed the best results with respect to bone formation/repair in CSBD. These results suggest that DBB plus 0.25% F1 can be used as a promising bioactive material for application in bone tissue engineering.

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BACKGROUND: Type 1 diabetes (T1D) is associated with delayed tissue healing and bone loss. Periodontal tissues during tooth movement (OTM) in T1D and under diabetic treatment are poorly understood. We aimed to study the effect of metformin as an add-on to insulin therapy on periodontal structures during OTM in T1D rats. METHODS: Rats were divided into normoglycemic (NG, n = 20) and streptozotocin-induced diabetic groups that were untreated (T1D, n = 20), treated with insulin (I-T1D, n = 20), or treated with insulin plus metformin (IM-T1D, n = 20). After 7 days of treatment, the first right upper molar (M1) was moved mesially. At days 0, 3, 7 and 14, the pattern of OTM and the periodontal tissues were analyzed by micro-CT, histomorphometry, and immunohistochemistry for TRAP. RESULTS: In T1D, major osteoclastogenic activity and bone loss versus other groups were confirmed by a greater TRAP-positive cell number and reabsorption surface on both the pressure and tension sides for 14 days (p < 0.01). Additionally, we observed low bone volume density. Metformin plus insulin resulted in a daily insulin dose reduction and major glycemic control versus I-T1D. Although no significant differences were observed between I-T1D and IM-T1D, the tooth displacement and inclination, periodontal ligament thickness, and alveolar bone density on the pressure side in IM-T1D were similar to that of NG (p > 0.05). CONCLUSION: Antidiabetic treatment reduces severe periodontal damage during applied orthodontic force in T1D untreated rats. Metformin as an add-on to insulin therapy resulted in glycemic control and a periodontal tissue response to orthodontic forces that was similar to that of normoglycemic rats.

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AIM: The effects of green tea on the modulation of vascularization during the progression of spontaneous periodontitis in long-term hyperglycaemia in streptozotocin-induced type 1 diabetic (T1D) rats were evaluated. MATERIALS AND METHODS: Wistar rats normoglycaemic (NG) and T1D were divided into two control groups, which received water (NG-W and T1D-W) and two experimental groups that received green tea (NG-GT and T1D-GT). Periodontal structures were evaluated by microtomographic and histological analyses. Number of immunostained cells for VEGF (NcVEGF+/mm2 ) and CD31 (NcCD31+/mm2 ), as well microvessel density (MVD) in the periodontal ligament (PDL) were evaluated. RESULTS: Long-term hyperglycaemia in T1D-W rats induced vascular alterations in PDL with a reduction of 36% in MVD, a decrease of 33% in NcCD31+/mm2 and an increase of 53% in NcVEGF+/mm2 . Concomitantly, a severe degree of periodontitis with higher reduction in bone volume and periodontal bone level was observed. In T1D-GT, green tea maintained the MVD, NcCD31+/mm2 and NcVEGF+/mm2 in the PDL similar to normoglycaemic groups. Clinically, in T1D-GT rats, green tea reduced dental plaque accumulation and the degree of periodontitis when compared to T1D-W. CONCLUSION: Daily green tea consumption has a therapeutic effect on the diabetic vascular disorder in PDL and the progression of periodontitis in long-term hyperglycaemia in T1D rats.

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A diabetes mellitus (DM) é um grupo de doenças metabólicas caracterizadas por hiperglicemia resultante do déficit na secreção e/ou ações de insulina. Dentre as muitas complicações da diabetes incluem a osteopenia diabética, que causa osteoporose e aumento do risco de fraturas ósseas. A patofisiologia da baixa resistência óssea associada a DM é considerada multifatorial, podendo ser decorrente da deficiência de insulina, resistência à insulina, insuficiência de osteoblastos, deficiência de vitamina D, formação e acúmulo dos produtos finais da glicação avançada e complicações microvasculares. Por isso, existe um interesse crescente no estudo da diabetes associada a outras alterações metabólicas e o efeito das drogas antidiabéticas, de forma a reverter os efeitos maléficos. O objetivo desse estudo foi avaliar a influência das drogas antidiabéticas na movimentação dentária ortodôntica e na densidade/microarquitetura óssea alveolar em ratos diabéticos. Assim, ratos Normoglicêmicos (NG,n=20) e Diabéticos induzidos pela estreptozotocina (DM1,n=60) foram divididos em: TinDM1(n=20) tratados com Insulina, TinmetDM1(n=20) tratados com Insulina+Metformina, e os STDM1(n=20) e STNG(n=20) que não receberam tratamento. Após 14 dias da indução, o 1o molar superior direito recebeu força ortodôntica (50g) em sentido mesial. Nos periodos experimentais de 0, 3, 7 e 14 dias, as maxilas foram coletadas e submetidas às análises microtomográficas para quantificar a movimentação dentária e a densidade óssea e histológica, para avaliar as alterações periodontais ocorridas durante a movimentação. Os dados microtomográficos foram submetidos à ANOVA a dois critérios e teste de Tukey (p<0,05). A indução com estreptozotocina induziu ao quadro de diabetes grave (glicemia de jejum de 325mg/dL) os quais foram acentuados com o tempo no grupo STDM1 (404mg/dL). A utilização de insulina e da associação insulina e metformina reduziram consideravelmente os níveis glicêmicos (127mg/dL)...

Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting in deficits in the secretion and/or insulin action. Among the many complications of diabetes, it includes diabetic osteopenia that causes osteoporosis and increased risk of bone fractures. The pathophysiology associated with low bone strength in DM is considered multifactorial and may be due to insulin deficiency, insulin resistance, osteoblast deficiency, vitamin D deficiency, formation and accumulation of advanced glycation end products and microvascular complications. Therefore, there is a growing interest in the study of diabetes associated with other metabolic abnormalities and the effect of antidiabetic drugs, in order to reverse the deleterious effects. The objective of this study was to evaluate the influence of antidiabetic drugs in orthodontic tooth movement and alveolar bone density/microarchitecture in diabetic rats. Thus, normoglycemic rats (NG, n=20) and streptozotocin-induced diabetic (DM1, n=60) were divided into TinDM1 (n=20) treated by insulin, TinmetDM1 (n=20) treated by Insulin + Metformin and STDM1 (n = 20) and STNG (n = 20) that received no treatment. After 14 days of induction, the M1 received orthodontic force (50g) to move mesially. After 0, 3, 7 and 14 days jaws were collected and subjected to microtomographic images analysis to quantify, tooth movement and bone density and histological analysis to evaluate periodontal changes occurred during the movement. Microtomographic data were submitted to two-way ANOVA and Tukey test (p <0.05). The induction with streptozotocin induced severe diabetes frame (fasting blood glucose 325 mg/dL) which accentuated over the time of the disease in STDM1 group (404mg/dL). The use of insulin and insulin and metformin reduced blood glucose levels to satisfactory values (127mg/dL). The strength of 50g applied on M1 promoted linear tooth movement, being lower in STNG group...

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