Effect of smear clear and some other commonly used irrigants on dislodgement resistance of mineral trioxide aggregate to root dentin

This study aimed to assess the push-out bond strength of mineral trioxide aggregate (MTA) to root canal dentin after irrigation with Smear Clear in comparison with 2.5% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX) and saline as commonly used root canal irrigants. The coronal and mid-root areas of maxillary anterior teeth were horizontally sectioned into one-millimeter thick slices. The root canal lumen of dentinal slices was dilated using a diamond bur with 1.3 mm diameter. After the application of MTA, the samples were incubated in 100% humidity for 10 minutes and were then randomly divided into four groups (n=20) and immersed in Smear Clear, 2.5% NaOCl, 2% CHX and saline for 30 minutes. No irrigant was used for the control group (n=20). A wet cotton pellet was placed on the samples and after 48 hours of incubation, push-out bond strength was measured using a universal testing machine. The samples were evaluated under a stereomicroscope to determine the mode of failure. One-way ANOVA was used to assess statistical differences among the groups. The control group showed the highest bond strength with significant differences with other groups (P0.05). Other pairwise comparisons showed no significant difference (P>0.05). Irrigation with Smear Clear, CHX and NaOCl did not cause a significant change in bond strength of MTA to dentin

Effects of Probiotics on Colitis-Induced Exacerbation of Alzheimer\u27s Disease in

Alzheimer’s disease (AD) is characterized by progressive cognitive decline and is a leading cause of death in the United States. Neuroinflammation has been implicated in the progression of AD, and several recent studies suggest that peripheral immune dysfunction may influence the disease. Continuing evidence indicates that intestinal dysbiosis is an attribute of AD, and inflammatory bowel disease (IBD) has been shown to aggravate cognitive impairment. Previously, we separately demonstrated that an IBD-like condition exacerbates AD-related changes in the brains of the AppNL-G-F mouse model of AD, while probiotic intervention has an attenuating effect. In this study, we investigated the combination of a dietary probiotic and an IBD-like condition for effects on the brains of mice. Male C57BL/6 wild type (WT) and AppNL-G-F mice were randomly divided into four groups: vehicle control, oral probiotic, dextran sulfate sodium (DSS), and DSS given with probiotics. As anticipated, probiotic treatment attenuated the DSS-induced colitis disease activity index in WT and AppNL-G-F mice. Although probiotic feeding significantly attenuated the DSS-mediated increase in WT colonic lipocalin levels, it was less protective in the AppNL-G-F DSS-treated group. In parallel with the intestinal changes, combined probiotic and DSS treatment increased microglial, neutrophil elastase, and 5hmC immunoreactivity while decreasing c-Fos staining compared to DSS treatment alone in the brains of WT mice. Although less abundant, probiotic combined with DSS treatment demonstrated a few similar changes in AppNL-G-F brains with increased microglial and decreased c-Fos immunoreactivity in addition to a slight increase in Aβ plaque staining. Both probiotic and DSS treatment also altered the levels of several cytokines in WT and AppNL-G-F brains, with a unique increase in the levels of TNFα and IL-2 being observed in only AppNL-G-F mice following combined DSS and probiotic treatment. Our data indicate that, while dietary probiotic intervention provides protection against the colitis-like condition, it also influences numerous glial, cytokine, and neuronal changes in the brain that may regulate brain function and the progression of AD

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Prospective, multicentre study of screening, investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland

Background: Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. Methods: We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (<135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration >10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. Results: 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was >3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I–III, modified Fisher 2–4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. Conclusions: In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care

Contribution Of Intestinal Dysfunction To Alzheimer’s Disease Progression

Longer life expectancies, due to advanced medical care, social, and environmental conditions, helped increase the number and percentage of Americans aging to ≥85. The number of individuals with Alzheimer’s disease (AD) age 65 or older is projected to be 7.1 and 13.8 million by 2025 and 2050, respectively. The total annual health care expense for AD patients is estimated to increase from $290 billion in 2019 to more than$1.1 trillion in 2050 (Association, 2019). Conclusively, AD is expected to become a more common cause of death and a major public health predicament due to aging of the baby boom generation in the United States. Extracellular Aβ plaque deposition resulting from successive proteolytic cleavage of amyloid precursor protein (APP), intracellular neurofibrillary tangles, and neuroinflammation are pathophysiologic features of AD correlating with cognitive decline, language impairment, memory loss, and ultimately, death. Due to the behavioral manifestation and the neurodegenerative hallmarks, AD is typically considered a brain specific disease. However, peripheral inflammatory changes such as increased serum levels of TNF-α, worsen cognitive decline in AD patients. This suggests that systemic inflammatory changes may cross-talk to the brain to influence disease. In support of this idea, long-term use of non-steroidal anti-inflammatory drugs (NSAID) decreases the risk of AD. Interestingly, colitis and colitis-associated colorectal cancer (CAC), which are characterized by accelerated levels of proinflammatory cytokines, induce anxiety, depression and cognitive/memory dysfunction in preclinical and clinical studies. Taken together, these studies suggest that peripheral immune changes influence AD progression in the brain. This dissertation consists of three related but separate studies aimed at understanding the impact of peripheral manipulations on brain pathology using AD mouse models. In our first study, we asked whether the liver-derived hormone, insulin like growth factor-1 (IGF-1), has effects in the brain to potentiate or attenuate disease using the AβPP/PS1 mutant mouse model of AD. To test this idea, we used a brain penetrant IGF-1R inhibitor. The second study shifts to focus on peripheral inflammatory manipulations to examine possible influences on disease. This study utilized a common colitis-like model of oral dextran sulfate sodium (DSS) to quantify brain and intestinal changes in the AppNL-G-F mutant knock-in mouse model of AD. The third study employed a more extensive intestinal inflammatory paradigm of colorectal tumorigenesis to also compare brain and intestinal changes using the AppNL-G-F mice. In the first study, the brain penetrant IGF-1R inhibitor (PPP, 1mg/kg/day) attenuated insoluble Aβ1-40/42 and pro-inflammatory cytokine levels (eotaxin, TNF-α, IL-1α, and IL-1β) in the temporal cortices of AβPP/PS1 mice. Additionally, an attenuation in microgliosis and protein p-tyrosine levels was observed due to drug treatment. Our data suggests IGF-1R signaling is associated with disease progression in this mouse model. More importantly, modulation of the brain IGF-1R signaling pathway was sufficient to attenuate aspects of disease phenotype. This suggested that small molecule therapy targeting liver-derived IGF-1 effects in the brain may be a viable intervention approach. In the second study, chronic intestinal inflammation, induced by dissolving 2% dextran sulfate sodium (DSS) in the drinking water, resulted in bloody diarrhea, disrupted colonic epithelium, and weight loss in wild type and AppNL-G-F male mice, changes similar to human inflammatory bowel disease (IBD). The inflammation correlated with increased levels of brain insoluble Aβ1-40/42 and decreased microglial CD68 immunoreactivity in DSS treated compared to vehicle treated AppNL-G-F mice. These data demonstrated that intestinal dysfunction is capable of altering plaque deposition and immune cell behavior in the brain. This study increased our understanding of the impact of peripheral inflammation on Aβ deposition and neuroinflammation in AD via an IBD-like model system. In the third study, azoxymethane (AOM)/DSS administration produced genotype and sex dependent colitis-associated colorectal cancer (CAC) symptomatic parameters in spleens and colons of wild type, App-/-, and AppNL-G-F mice. As expected, AOM/DSS treatment exacerbated Aβ plaque load in male AppNL-G-F mice. Interestingly, AOM/DSS treated male AppNL-G-F mice also demonstrated worsened intestinal inflammation and increased colonic tumorigenesis compared to wild types. However, AppNL-G-F female mice were protected against intestinal inflammation and tumorigenesis as well as any exacerbation of brain Aβ plaque load. These data demonstrated that the AD-associated autosomal dominant mutations of APP introduced into the AppNL-G-F mouse line provide protection against intestinal disease as well as brain exacerbation in a sex-selective fashion. Collectively, studies in this dissertation demonstrate that peripheral stimuli, whether hormonal or inflammatory, appear capable of altering disease phenotype in two commonly used mouse models of AD. In addition, there may be sex-selectivity of this peripheral to brain communication during disease. One conclusion from this work is that manipulations of peripheral events may be sufficient to alleviate brain changes in AD. This suggests the exciting possibility that therapeutic interventions need not penetrate into the brain to offer benefit

Revascularization Treatment of Immature Permanent Tooth with Necrotic Pulp: A Case Report

Introduction: Revascularization is the newest treatment proposed for an immature permanent tooth with necrotic pulp. Revascularization is defined as a treatment process with a biological base which is aimed at replacing the lost structures and the continued development of roots. Case presentation: Patient was an eight-year-old child with the history of trauma to the maxillary anterior region. After clinical and radiographic evaluations, tooth #9 was diagnosed with the pulp necrosis, and revascularization was carried out according to Banch and Trope principles. Conclusion: The clinical and radiographic evaluation after treatment revealed no signs and symptoms and root development was in progress which was an indication of successful treatment. It seems that, in the case of proper selection of the patient, this method can be an appropriate replacement for apexification in immature teeth with pulp necrosis

Soft-tissue esthetic outcome of single implants: Immediate placement in fresh extraction sockets versus conventional placement in healed sockets

Background: Immediate implant placement has advantages such as requiring fewer surgical procedures and decreased treatment time; however, unpredictable soft- and hard-tissue outcome is a problem. This study aimed to compare the soft-tissue esthetic outcome of single implants placed in fresh extraction sockets versus those placed in healed sockets. Materials and Methods: This cross-sectional, retrospective study was performed on 42 patients who received single implants. Twenty-two patients with a mean age of 40.14 years received immediate implants while 18 patients with a mean age of 43.40 years were subjected to conventional (delayed) implant placement. The mean follow-up time was 14.42 ± 8.37 months and 18.25 ± 7.10 months in the immediate and conventional groups, respectively. Outcome assessments included clinical and radiographic examinations. The esthetic outcome was objectively rated using the pink esthetic score (PES). Results: All implants fulfilled the success criteria. The mean PES was 8.54 ± 1.26 and 8.10 ± 1.65 in the immediate and conventional groups, respectively. This difference was not statistically significant (P = 0.329). The two PES parameters, namely, the facial mucosa curvature and facial mucosa level had the highest percentage of complete score. Conclusions: Immediate and conventional single implant treatments yielded comparable esthetic outcomes

Effect of CO2 Laser-Assisted Titanium Tetra-fluoride on Demineralization of Enamel Around Orthodontic Brackets: Effect of laser on demineralized tooth

Introduction: One of the clinical problems following orthodontic treatment is white spot lesions around orthodontic brackets due to enamel demineralization. Confronting enamel demineralization during fixed treatments has long been a challenge for orthodontists. The aim of this in vitro study was to evaluate the effect of CO2 laser and Titanium Tetra-fluoride (TiF4) application on the prevention of enamel demineralization around orthodontic brackets.Methods: Eighty permanent premolars were selected and bonded with brackets. They were randomly divided into four groups (n=20): topical titanium tetra-fluoride gel 4% (TiF4), CO2 laser (10.6 μm wavelength for 10 seconds, peak power=291 W), fluoride+laser (F+L), and control (C). All specimens were demineralized for 10 days in a 0.2 M acetate buffer solution. The mean lesion depths were determined by using polarized light microscopy.Results: The mean depth of lesion was the highest in the C group and then decreased in the TiF4, CO2laser, and F+L groups, respectively. The difference between all groups was significant (P<0.05), except for the CO2 laser and F+L groups.Conclusion: The lowest amount of demineralization around the orthodontic brackets was observed in the L+F group, followed by the CO2 laser, TiF4, and control groups, respectivel

The effects of valproic acid on the mRNA expression of Natriuretic Peptide Receptor A and KQT-like subfamily Q-1 in human colon cancer cell lines

Aim and objectives: The histone deacetylase (HDAC) inhibitor, Valproic Acid (VPA), causes growth inhibition and apoptosis in colorectal cancer cells. HDAC inhibition is associated with the transcriptional regulation of Natriuretic Peptide Receptor-A (NPR-A). NPR-A regulates voltage-gated potassium channel, KQT-like subfamily Q, member 1 (KCNQ1). NPR-A and KCNQ1 are also involved in the initiation and propagation of cancer cells. In this study, we investigated the simultaneous expressional changes of NPR-A and KCNQ1 among VPA-treated colon cancer cells. Materials and methods: Human colorectal cancer cells were cultured and treated with increasing concentrations of VPA at different time points. MTT viability test was conducted to evaluate the growth inhibition. Real Time RT-PCR was used to quantify differential mRNA expression of NPR-A and KCNQ1 genes. Two-way ANOVA and bonferroni post-tests were used to analyze data statistically. Results: We showed that VPA treatment inhibits the growth of SW-480 cells more efficiently compared to HT-29. NPR-A and KCNQ1 genes were significantly upregulated upon VPA treatment in both cell lines (P < 0.0001). Conclusion: The alteration of NPR-A and KCNQ1 genes were more ordered among SW-480 cancer cells. The expressional changes of KCNQ1 and NPR-A among VPA treated human colon cancer cells follow the same pattern in similar combinations. VPA could regulate the expression of KCNQ1 through altering the mRNA expression of NPR-A