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Τρίτη 19 Ιουλίου 2022

TREM2‐induced activation of microglia contributes to synaptic integrity in cognitively intact aged individuals with Alzheimer's neuropathology

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TREM2-induced activation of microglia contributes to synaptic integrity in cognitively intact aged individuals with Alzheimer's neuropathology

Efficient TREM2-phagocytic microglia underlie synaptic resilience in NDAN, removing damaged synpases, contributing to synaptic integrity and protecting from memory deficits.


Abstract

The existence of individuals who remain cognitively intact despite presenting histopathological signs of Alzheimer's disease (AD), here referred to as "Nondemented with AD neuropathology" (NDAN), suggests that some mechanisms are triggered to resist cognitive impairment. Exposed phosphatidylserine (ePS) represents a neuronal "eat-me" signal involved in microglial-mediated phagocytosis of damaged synapses. A possible mediator of this process is TREM2, a microglial surface receptor activated by ligands including PS. Based on TREM2 role in the scavenging function of microglia, we hypothesize that an efficient microglial phagocytosis of damaged synapses underlies synaptic resilience in NDAN, thus protecting from memory deficits. Using immunofluorescence microscopy, we performed a comparative study of human post-mortem frontal cortices of aged-matched, AD and NDAN individuals. We studied the distribution of activated microglia (IBA1, IBA1+/CD68+ cells) and phagocytic microglia-related proteins (TREM2, DAP12), demonstrating higher microglial activation and TREM2 expression in NDAN versus AD. A study of the preservation of synapses around plaques, assessed using MAP2 and βIII tubulin as dendritic and axonal markers, respectively, and PSD95 as a postsynaptic marker, revealed preserved axonal/dendritic structure around plaques in NDAN versus AD. Moreover, high levels of PSD95 around NDAN plaques and the colocalization of PSD95 with CD68 indicated a prompt removal of damaged synapses by phagocytic microglia. Furthermore, Annexin V assay on aged-matched, AD and NDAN individuals synaptosomes revealed increased levels of ePS in NDAN, confirming damaged synapses engulfment. Our results suggest a higher efficiency of TREM2-induced phagocytic microglia in removing damaged synapses, underlying synaptic resilience in NDAN individuals.
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Ridge augmentation using autologous concentrated growth factors enriched bone graft matrix versus guided bone regeneration using native collagen membrane in horizontally deficient maxilla: A randomized clinical trial

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Abstract

Background

Facial resorption of maxillary alveolar ridges is a challenging situation for implant rehabilitation, which mandates a preparatory surgery of bone augmentation. Guided bone regeneration using a 1:1 mixture of autogenous particulate and anorganic bovine bone mineral (ABBM) showed reliable outcomes in treating horizontally deficient ridges.

Methods

Twenty-eight patients were randomly assigned into two groups; in the control group, the 1:1 mixture of particulate autogenous bone and ABBM was covered with native collagen membrane, while in the study group, it was mixed with autologous fibrin glue (AFG) to make a sticky bone that was covered by concentrated growth factor (CGF) membrane. For each proposed implant site, the average bone width gain was calculated preoperatively, immediately after augmentation and after 6 months. Implants were placed after 6 months and the implant stability quotient (ISQ) was measured after insertion and after 6 more months.

Results

The graft consolidation period went uneventful in both groups; however, two cases in the sticky bone group showed total resorption of the graft upon re-entry. The mean horizontal bone width after 6 months was 9 mm ± 0.71 in the guided bone regeneration (GBR) group which was higher than 7.9 mm ± 0.92 for the sticky bone group. The mean primary stability was higher in the GBR group; 67.19 ± 2.23 compared to 66.7 ± 3.22 for the sticky bone group, while the mean secondary stability was higher in the sticky bone group; 72 ± 2.15 compared to 71.7 ± 2.27 for the GBR group. Results of Shapiro–Wilk's for bone width data and model residuals were both statistically not significant (p > 0.05).

Conclusion

Comparing CGF membrane versus native collagen membrane as barriers for GBR showed no statistically significant difference regarding bone gain. However, from a clinical point of view, CGF membrane is not a predictable barrier for guided bone regeneration.
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Early marginal bone loss around dental implants to define success in implant dentistry: A retrospective study

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Abstract

Purpose

The aim of this study was to establish an objective criterion in terms of marginal bone level (MBL) to know the prognosis of an implant.

Materials and Methods

A group of 176 patients in whom 590 implants were placed were included in this retrospective study. Patients older than 18 years, presenting either Kennedy class I or II edentulous section, or totally edentulous at least in one of the dental arches were included in this study. Those with any type of disturbance able to alter bone metabolism or with nontreated periodontal disease were excluded. Data on radiographic MBL at loading, 6 and 18 months later, age, gender, smoking habits, history of periodontitis, bone substratum, implant, and prosthetic features were recorded. Nonparametric receiver operating curves (ROC) were constructed for the MBL at 18 months in order to establish a distinction among high bone loser (HBL) and low bone loser (LBL) implants. Differences as a function of main variables were also determined, particularly abutment height and periodontal disease.

Results

HBL implants lost at least 0.48 mm of MBL 6 months after loading; they reached at least 2 mm of MBL 18 months after loading. MBL rate followed a nonlinear trend, except in implants restored over long prosthetic abutments and in patients with history of severe periodontitis; in whom the rate of MBL over the time was nearly zero.

Conclusion

Implants that lose more than 0.5 mm of marginal bone 6 months after loading are at great risk of not being radiographically successful anymore. Therefore, 0.5 mm of MBL is proposed as a distinctive and objective criterion of success in Implant Dentistry within a 6-month follow-up period. A prosthetic abutment height ≥2 mm resulted the most protective factor in the peri-implant bone maintenance.
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Camrelizumab plus chemotherapy in advanced non‐squamous non‐small cell lung cancer: Treatment response, survival pattern, and safety

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Camrelizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer: Treatment response, survival pattern, and safety

This study retrospectively analysed 31 driver-gene-negative advanced non-squamous non-small cell lung cancer (NSCLC) patients who received a 21-day therapy cycle for four cycles of camrelizumab (intravenous injection, 200 mg/cycle) plus carboplatin and pemetrexed (CP) chemotherapy, followed by maintenance therapy using camrelizumab or pemetrexed or camrelizumab plus pemetrexed. Another 40 patients who underwent CP chemotherapy were retrieved as control group. Interestingly, objective response rate (ORR) was elevated in camrelizumab plus CP group compared to CP group (58.1% vs. 32.5%), while disease control rate (DCR) was of no difference between those two groups (83.9% vs. 72.5%). Camrelizumab plus CP achieved a prolonged progression-free survival (PFS) compared with CP alone (11.0 (95% CI: 9.1–12.9) months versus 7.2 (95% CI: 5.1–9.3) months), also realized an increasing overall survival (OS) trend (without statistical significance; 19.3 (95% CI: 15.4–23.2) months versu s 15.1 (95% CI: 13.9–16.3) months). Further multivariate Cox's regression analysis exhibited that camrelizumab plus CP (vs. CP) independently related to prolonged PFS and OS. Moreover, the most common adverse events related to camrelizumab plus CP were fatigue (45.2%), peripheral neuropathy (35.5%), nausea and vomiting (35.5%); furthermore, most adverse events were controllable. Collectively, camrelizumab plus chemotherapy exhibits good efficacy and manageable adverse events in treating advanced non-squamous NSCLC patients.


Abstract

What is known and objective

Camrelizumab, a humanized monoclonal programmed cell death protein-1 antibody independently developed by China, is introduced as a treatment selection for non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of camrelizumab plus chemotherapy in treating advanced non-squamous NSCLC patients.

Methods

This study retrospectively analysed 31 driver-gene-negative advanced non-squamous NSCLC patients who received a 21-day therapy cycle for four cycles of camrelizumab (intravenous injection, 200 mg/cycle) plus carboplatin and pemetrexed (CP) chemotherapy, followed by maintenance therapy using camrelizumab or pemetrexed or camrelizumab plus pemetrexed. Another 40 patients who underwent CP chemotherapy were retrieved as control group.

Results and discussion

The objective response rate (ORR) was elevated in camrelizumab plus CP group compared to CP group (58.1% vs. 32.5%, p = 0.031), while disease control rate (DCR) was of no difference between those two groups (83.9% vs. 72.5%, p = 0.255). Camrelizumab plus CP achieved a prolonged PFS compared with CP alone (median: 11.0 (95% CI: 9.1–12.9) months versus 7.2 (95% CI: 5.1–9.3) months, p = 0.026), also realized an increasing OS trend (without statistical significance; 19.3 (95% CI: 15.4–23.2) months versus 15.1 (95% CI: 13.9–16.3) months, p = 0.093). Further multivariate Cox's regression analysis exhibited that camrelizumab plus CP (vs. CP) independently related to prolonged PFS (p < 0.001) and OS (p = 0.027). Moreover, the most common adverse events related to camrelizumab plus CP were fatigue (45.2%), peripheral neuropathy (35.5%), nausea and vomiting (35.5%); furthermore, most a dverse events were controllable.

What is new and conclusion

Camrelizumab plus chemotherapy exhibits good efficacy and manageable adverse events in treating advanced non-squamous NSCLC patients.
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Detecting and Managing Partial Shorts in Cochlear Implants: A Validation of Scalp Surface Potential Testing

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Abstract

Objective

To investigate the value of scalp surface potentials to identify and manage partial short circuits to ground in cochlear implant electrodes.

Design

A retrospective review of patients with suspected partial short circuits.

Main outcome measure

Electrical output of individual electrodes was measured using scalp surface potentials for patients reporting a change in hearing function. Electrical output was compared to functional performance and impedance measurements to determine if devices with suspected partial short circuits were experiencing a decrease in performance as a result of reduced electrical output. Electrical output was checked in an artificial cochlea for two implants following explant surgery to confirm scalp surface potential results.

Results

All patients with suspected partial short circuits (n=49) had reduced electrical output, a drop in impedances to approximately ½ of previously stable measurements or to below 2 kOhms, an atypical electrical field measurement (EFI) and a decline in hearing function. Only devices with an atypical EFI showed reduced electrical output. Results of scalp based surface potentials could be replicated in an artificial cochlea following explantation of the device. All explant reports received to date (n=42) have confirmed partial short circuits, with an additional 4 devices failing integrity tests.

Conclusion

Surface potential measurements can detect partial shorts and had 100% correlation with atypical EFI measurements, which are characteristic of a partial short to ground in this device. Surface potentials can help determine the degree to which the electrode array is affected, particularly when behavioural testing is limited or not possible.
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Bead‐anchored surgical templates for static computer‐assisted implant surgery (s‐CAIS) – A dental technique

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Abstract

This technique report describes an alternative method to stabilize surgical templates throughout full-arch static computer-assisted implant surgery (FA s-CAIS). In FA s-CAIS, remaining teeth, mucosa, existing implants, custom occlusal device, bone, or any combination thereof, could be used as an initial positioning mechanism to position surgical templates. Different anchoring mechanisms are then used to stabilize the surgical templates during surgery. In this report, a novel design of surgical templates using remaining dentition and opposing occlusal surfaces as initial positioning mechanism followed by the combination of bone block fixation screw and stainless-steel beads as secondary anchoring mechanisms is described. The advantages, limitations, and comparisons with surgical templates using other anchoring mechanisms are also discussed.

This article is protected by copyright. All rights reserved
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The malignant property of circHIPK2 for angiogenesis and chemoresistance in non-small cell lung cancer

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Publication date: Available online 19 July 2022

Source: Experimental Cell Research

Author(s): Mingming Ren, Xiang Song, Jieting Niu, Guojie Tang, Zhen Sun, Yanguang Li, Fanyi Kong
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Orthopedic Surgery Causes Gut Microbiome Dysbiosis and Intestinal Barrier Dysfunction in Prodromal Alzheimer Disease Patients: A Prospective Observational Cohort Study

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imageObjective: To investigate gut microbiota and intestinal barrier function changes after orthopedic surgery in elderly patients with either normal cognition (NC) or a prodromal Alzheimer disease phenotype (pAD) comprising either subjective cognitive decline (SCD) or amnestic mild cognitive impairment (aMCI). Background: Homeostatic disturbances induced by surgical trauma and/or stress can potentially alter the gut microbiota and intestinal barrier function in elderly patients before and after orthopedic surgery. Methods: In this prospective cohort study, 135 patients were subject to preoperative neuropsychological assessment and then classified into: NC (n=40), SCD (n=58), or aMCI (n=37). Their gut microbiota, bacterial endotoxin (lipopolysaccharide), tight junction (TJ) protein, and inflammatory cytokines in blood were measured before surgery and on postsurgical day 1, 3, and 7 (or before discharge). Results: The short-chain fatty acid (SCFA)-producing bacteria were lower while the gram-negative bacteria, lipopolysaccharide and TJ were higher preoperatively in both the SCD and aMCI (pAD) groups compared with the NC group. After surgery, a decrease in SCFA-producing bacteria, and an increase in both gram-negative bacteria and plasma claudin were significant in the pAD groups relative to the NC group. SCFA-producing bacteria were negatively correlated with TJ and cytokines in pAD patients on postsurgical day 7. Furthermore, surgery-induced perioperative metabolic stress and inflammatory responses were associated with gut microbiota alterations. Conclusions: Surgery exacerbates both preexisting microbiota dysbiosis and intestinal barrier dysfunction in pAD patients, all of which may be associated with systemic inflammation and, in turn, may lead to further cognitive deterioration.
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NUT carcinoma of the mandible in a child: case report and systematic review

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This report illustrates the management of mandibular NUT carcinoma in a pediatric patient, complemented by a systematic review of head and neck NUT carcinoma. A 5-year-old female presented with an enlarging jaw mass that was diagnosed as BRD4-NUTM1 carcinoma and was treated with hemimandibulectomy and chemoradiation. (Source: International Journal of Oral and Maxillofacial Surgery)
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Δευτέρα 18 Ιουλίου 2022

Allopurinol‐induced Stevens‐Johnson syndrome and toxic epidermal necrolysis: Signal detection and preventability from Vietnam National pharmacovigilance database

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Allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: Signal detection and preventability from Vietnam National pharmacovigilance database

Among 72,822 spontaneous ADR reports submitted to the Vietnam National Drug Information and Adverse Drug Reaction Monitoring Centre, 392 reports were on SJS/TEN, of which, 65 cases (16.6%) were related to allopurinol. The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 (ROR of 3.531, 95% CI: 1.830–6.810) and annually increased until 2019 (ROR of 11.923, 95% CI: 8.508–16.710). The preventability assessment showed that no allopurinol-induced SJS/TEN case was definitely unpreventable. 61.6% of the SJS/TEN cases were avoidable because they were associated with inappropriate prescribing such as unapproved indications, too high initial dose and even rechallenging in patients with a history of allopurinol allergy.


Abstract

What Is Known and Objective

Allopurinol, the first-line medication for hyperuricemia is well-known for its association with severe cutaneous adverse reactions, especially Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In the current study, we analysed the Vietnamese spontaneous reporting database to identify signals and preventability of allopurinol-induced SJS/TEN in Vietnam from 2010 to 2019.

Methods

Signal generation was assessed using the case/non-case method. Reporting odds ratios (RORs) and 95% confidence intervals (95% CI) were calculated.

Results

Among 72,822 spontaneous ADR reports submitted to the Vietnam National Drug Information and Adverse Drug Reaction Monitoring Centre, 392 reports were on SJS/TEN, of which, 65 cases (16.6%) were related to allopurinol. The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 (ROR of 3.531, 95% CI: 1.830–6.810) and annually increased until 2019 (ROR of 11.923, 95% CI: 8.508–16.710). The preventability assessment showed that no allopurinol-induced SJS/TEN case was definitely unpreventable. 61.6% of the SJS/TEN cases were avoidable because they were associated with inappropriate prescribing such as unapproved indications, too high initial dose and even rechallenging in patients with a history of allopurinol allergy.

What Is New and Conclusion

The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 and annually increased until 2019. Our first report specifically focusing on the ADR preventability of allopurinol showed that correction of medical errors relating to prescription could prevent more than 60% of SJS/TEN cases in Vietnamese allopurinol users. This is a feasible and practical solution, provided that there would be a systematic change in both healthcare systems and public awareness.
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