Presynaptic Kainate Receptors onto Somatostatin Interneurons Are Recruited by Activity throughout Development and Contribute to Cortical Sensory Adaptation.

Somatostatin (SST) interneurons produce delayed inhibition because of the short-term facilitation of their excitatory inputs created by the expression of metabotropic glutamate receptor 7 (mGluR7) and presynaptic GluK2-containing kainate receptors (GluK2-KARs). Using mice of both sexes, we find that as synaptic facilitation at layer (L)2/3 SST cell inputs increases during the first few postnatal weeks, so does GluK2-KAR expression. Removal of sensory input by whisker trimming does not affect mGluR7 but prevents the emergence of presynaptic GluK2-KARs, which can be restored by allowing whisker regrowth or by acute calmodulin activation. Conversely, late trimming or acute inhibition of Ca2+/calmodulin-dependent protein kinase II is sufficient to reduce GluK2-KAR activity. This developmental and activity-dependent regulation also produces a specific reduction of L4 GluK2-KARs that advances in parallel with the maturation of sensory processing in L2/3. Finally, we find that removal of both GluK2-KARs and mGluR7 from the synapse eliminates short-term facilitation and reduces sensory adaptation to repetitive stimuli, first in L4 of somatosensory cortex, then later in development in L2/3. The dynamic regulation of presynaptic GluK2-KARs potentially allows for flexible scaling of late inhibition and sensory adaptation.SIGNIFICANCE STATEMENT Excitatory synapses onto somatostatin (SST) interneurons express presynaptic, calcium-permeable kainate receptors containing the GluK2 subunit (GluK2-KARs), activated by high-frequency activity. In this study we find that their presence on L2/3 SST synapses in the barrel cortex is not based on a hardwired genetic program but instead is regulated by sensory activity, in contrast to that of mGluR7. Thus, in addition to standard synaptic potentiation and depression mechanisms, excitatory synapses onto SST neurons undergo an activity-dependent presynaptic modulation that uses GluK2-KARs. Further, we present evidence that loss of the frequency-dependent synaptic components (both GluK2-KARs and mGluR7 via Elfn1 deletion) contributes to a decrease in the sensory adaptation commonly seen on repetitive stimulus presentation.

Murine orthotopic lung transplant models: A comprehensive overview of genetic mismatch degrees and histopathological insights into chronic lung allograft dysfunction.

Currently, lung transplantation outcome remains inferior compared to other solid organ transplantations. A major cause for limited survival after lung transplantation is chronic lung allograft dysfunction. Numerous animal models have been developed to investigate chronic lung allograft dysfunction to discover adequate treatments. The murine orthotopic lung transplant model has been further optimized over the last years. However, different degrees of genetic mismatch between donor and recipient mice have been used, applying a single, minor, moderate, and major genetic mismatch. This review aims to reassess the existing murine mismatch models and provide a comprehensive overview, with a specific focus on their eventual histopathological presentation. This will be crucial to leverage this model and tailor it according to specific research needs.

Methylene blue-assisted molecularly-imprinted film modified nitrogen and sulfur co-doped molybdenum carbide for simultaneous electrochemical determination of two hepatotoxic drugs.

A novel electrochemical sensor with a dual-template molecular imprinting technology was fabricated for the simultaneous detection of paracetamol (PAR) and isoniazid (INZ). The sensor was constructed using nitrogen and sulfur co-doped molybdenum carbide (N, S@Mo2C) and a thin layer of electro-polymerized methylene blue was applied onto the surface of the N, S@Mo2C. The electrochemical sensor demonstrated remarkable analytical efficiency for the concurrent PAR and INZ quantification under optimal circumstances. The system achieved an exceptionally low limit of detection (S/N = 3) of  3.7 nM for PAR, with a concentration range  of  0.013 and 140 µM.  A LOD of 7.6 nM was attained for INZ, with a linear range  between 0.025 and 140 µM. Furthermore, the platform's selectivity was evaluated using differential pulse voltammetry  (DPV). The designed platform successfully detected PAR and INZ in authentic samples with recoveries varying between 98.3% and 104.9%. The relative standard deviations (RSD) for these measurements ranged from 2.7 to 4.0%, demonstrating that the proposed sensor is extremely stable, repeatable, and reproducible. These promising results suggest that the sensor holds potential for the detection of various (bio) molecules, paving the way for future applications in sensing fields.

Current Strategies for Treatment of Mandibular Fractures With Plate Osteosynthesis: A European Prospective Study.

PURPOSE: The training and preferences of surgeons influence the type of surgical treatment for mandibular fractures. This multicentre prospective study analyzed the current treatment strategies and outcomes for mandibular fractures with open reduction and internal fixation (ORIF). MATERIAL AND METHODS: This prospective study included patients aged ≥16 years who underwent ORIF for mandibular fractures in 12 European maxillofacial centers. Age, sex, pretrauma dental status, fracture cause, site and type, associated facial fractures, surgical approach, plate number and thickness (≤1.4 or ≥1.5 mm), duration of postoperative maxillomandibular fixation, occlusal and infective complications at 6 weeks and 3 months, and revision surgeries were recorded. RESULTS: Between May 1, 2021 and April 30, 2022, 425 patients (194 single, 182 double, and 49 triple mandibular fractures) underwent ORIF for 1 or more fractures. Rigid osteosynthesis was performed for 74% of fractures and was significantly associated with displaced ( P =0.01) and comminuted ( P =0.03) fractures and with the number of nonsurgically treated fracture sites ( P =0.002). The angle was the only site associated with nonrigid osteosynthesis ( P <0.001). Malocclusions (5.6%) and infective complications (5.4%) were not associated with osteosynthesis type. CONCLUSION: Rigid osteosynthesis was the most frequently performed treatment at all fracture sites, except the mandibular angle, and was significantly associated with displaced and comminuted fractures and the number of nonsurgically treated fracture sites. No significant differences were observed regarding postoperative malocclusion or infections among osteosynthesis types.

Heavy metals accumulation in the meat, kidney and liver of cattle, broilers and goats sold in Quetta, northwestern city of Balochistan, Pakistan.

1. It was assumed that the concentrations of arsenic (As), chromium (Cr), cobalt (Co), lead (Pb), manganese (Mn) and mercury (Hg) in the meat, kidney and liver of cattle, broilers and goats within Quetta city potentially exceeded the permissible limits for heavy metal content. Risk assessment of these heavy metals on human health were estimated based on daily intake (EDI), target hazard quotient (THQ) and hazard index (HI).2. Samples of the meat, liver and kidney of cattle, broilers and goats were collected from butcher shops and slaughterhouses in 20 different areas of Quetta city. Overall, 180 samples were analysed, each for six heavy metals. After acid digestion of meat samples, heavy metals analysis was carried out via atomic absorption spectroscopy.3. The results varied in levels depending upon the species and organ type. The average concentrations of As, Pb and Hg were within the established reference limits of the Australia New Zealand Food Authority (ANZFA 2015) and the European Commission (EC, 2006), although some samples exceeded these limits. Compared with the kidney and meat, the liver was the primary tissue for Cr, Pb and Hg bioaccumulation. Metals concentration were mostly within the normal range in samples from cattle and goats, while the Mn concentration was elevated in broilers.4. The estimated daily intake (EDI) revealed that the intake of As, Co, Pb and Hg was mainly derived from goat and cattle products, whereas broiler samples were more contaminated with Cr and Mn. The EDIs of Cr and Hg in adults exceeded the oral reference dose, referring to potential adverse effects. The EDIs for Co and Mn were low, suggesting that additional intake sources were necessary. Except for As, none of the determined elements had a target hazard quotient (THQ) above 1.

Systemic Immune-Inflammation Index in Relation to Diabetes Markers in Saudi Adults: A Retrospective Study.

Background and objectives: Low-grade inflammation is associated with metabolic disturbances like diabetes. The systemic immune-inflammation index (SII) has been proposed as a predictive tool to identify individuals at a greater risk of diabetes. This study aims to examine the association between SII and diabetes markers. Method and materials: We used retrospective data from a large cohort of adults (n = 3895) aged ≥18 in Saudi Arabia. The SII was calculated, and the markers of diabetes such as fasting blood glucose (FBG), insulin, and hemoglobin A1c (HbA1c) were included. Results: Across the quartiles of SII, FBG, insulin, and HbA1c were significantly higher in adults with higher compared to lower SII (p < 0.0001, p = 0.04, p < 0.0001, respectively). A two SD higher FBG was significantly associated with an SII difference of 47.7 (95% CI: (15.5, 91.9)). In subgroup analysis, this relationship prevailed in normal-weight participants and among those with normoglycemia and prediabetes but was attenuated in participants with diabetes. The association also prevailed in separate analyses for males and females but was stronger among females. Linear regression models showed no significant association between insulin, HbA1c, and SII. Conclusions: SII was associated with the markers of diabetes. The utility of SII for predicting diabetes can be confirmed with prospective cohort studies.

Oral contraceptive pills shortage in Lebanon amidst the economic collapse: a nationwide exploratory study.

BACKGROUND: The political instability, economic crisis, and devaluation of the national currency left Lebanese females suffering from a scarcity of oral contraceptive pills (OCPs). Therefore, we aimed to identify the incidence of OCPs shortage in Lebanon and its impact on women's sexual and reproductive health, as well as physical and psychological well-being. METHODS: Community pharmacies were selected randomly across Lebanon, using a stratified sampling approach, where female clients asking for OCPs were interviewed using a standardized data collection form. RESULTS: A total of 440 females were interviewed. More than three-quarters of the participants (76.4%) reported not finding their preferred OCPs brands, almost 40% were affected by the increased prices, and 28.4% declared stockpiling OCPs. More than half of the participants using OCPs for pregnancy prevention reported adopting alternative traditional contraceptive methods (55.3%). Unplanned pregnancy was reported by 9.5% of participants, where 75% of them disclosed intentional abortion while the remaining (25%) reported experiencing a spontaneous miscarriage. Other consequences of OCPs shortage included mood disturbances (52.3%), dysregulation of menses (49.7%), dysmenorrhea (21.1%), weight gain (19.6%), acne (15.7%), and hirsutism (12.5%). Of the participants taking OCPs for birth control, 48.6% reported a reduced frequency of sexual intercourse, which led to conflicts with their partners (46%) and a decreased libido (26.7%). CONCLUSIONS: OCPs shortage has seriously and negatively exposed women to various undesirable consequences including unplanned pregnancy and dysregulation of menses. Therefore, there is an urgent need to bring the attention of healthcare authorities to support the national pharmaceutical industry in manufacturing affordable OCPs generics to meet women's reproductive health demands.

Ratiometric fluorometric determination of sulfide using graphene quantum dots and self-assembled thiolate-capped gold nanoclusters triggered by aluminum.

A ratiometric-based fluorescence emission system was proposed for the determination of sulfide. It consists of blue emissive graphene quantum dots (GQDs) and self-assembled thiolate-protected gold nanoclusters driven by aluminum ion (Al3+@GSH-AuNCs). The two types of fluorophores are combined to form a ratiometric emission probe. The orange emission of Al3+ @GSH-AuNCs at 624 nm was quenched in the presence of sulfide ion owing to the strong affinity between sulfide and Au(I), while the blue GQDs fluorescence at 470 nm remained unaffected. Interestingly, the Al3+@GSH-AuNCs and GQDs were excited under the same excitation wavelength (335 nm). The response ratios (F470/F624) are linearly proportional to the sulfide concentration within the linear range of 0.02-200 µM under the optimal settings, with a limit of detection (S/N = 3) of 0.0064 µM. The proposed emission probe was applied to detect sulfide ions in tap water and wastewater specimens, with recoveries ranging from 95.3% to 103.3% and RSD% ranging from 2.3% to 3.4%, supporting the proposed method's accuracy.

A Novel Rabbit Model of Retained Hemothorax with Pleural Organization.

Retained hemothorax (RH) is a commonly encountered and potentially severe complication of intrapleural bleeding that can organize with lung restriction. Early surgical intervention and intrapleural fibrinolytic therapy have been advocated. However, the lack of a reliable, cost-effective model amenable to interventional testing has hampered our understanding of the role of pharmacological interventions in RH management. Here, we report the development of a new RH model in rabbits. RH was induced by sequential administration of up to three doses of recalcified citrated homologous rabbit donor blood plus thrombin via a chest tube. RH at 4, 7, and 10 days post-induction (RH4, RH7, and RH10, respectively) was characterized by clot retention, intrapleural organization, and increased pleural rind, similar to that of clinical RH. Clinical imaging techniques such as ultrasonography and computed tomography (CT) revealed the dynamic formation and resorption of intrapleural clots over time and the resulting lung restriction. RH7 and RH10 were evaluated in young (3 mo) animals of both sexes. The RH7 recapitulated the most clinically relevant RH attributes; therefore, we used this model further to evaluate the effect of age on RH development. Sanguineous pleural fluids (PFs) in the model were generally small and variably detected among different models. The rabbit model PFs exhibited a proinflammatory response reminiscent of human hemothorax PFs. Overall, RH7 results in the consistent formation of durable intrapleural clots, pleural adhesions, pleural thickening, and lung restriction. Protracted chest tube placement over 7 d was achieved, enabling direct intrapleural access for sampling and treatment. The model, particularly RH7, is amenable to testing new intrapleural pharmacologic interventions, including iterations of currently used empirically dosed agents or new candidates designed to safely and more effectively clear RH.

Manual versus rigid intraoperative maxillo-mandibular fixation in the surgical management of mandibular fractures: A European prospective analysis.

PURPOSE: Intraoperative stabilisation of bony fragments with maxillo-mandibular fixation (MMF) is an essential step in the surgical treatment of mandibular fractures that are treated with open reduction and internal fixation (ORIF). The MMF can be performed with or without wire-based methods, rigid or manual MMF, respectively. The aim of this study was to compare the use of manual versus rigid MMF, in terms of occlusal outcomes and infective complications. MATERIALS AND METHODS: This multi-centric prospective study involved 12 European maxillofacial centres and included adult patients (age ≥16 years) with mandibular fractures treated with ORIF. The following data were collected: age, gender, pre-trauma dental status (dentate or partially dentate), cause of injury, fracture site, associated facial fractures, surgical approach, modality of intraoperative MMF (manual or rigid), outcome (minor/major malocclusions and infective complications) and revision surgeries. The main outcome was malocclusion at 6 weeks after surgery. RESULTS: Between May 1, 2021 and April 30, 2022, 319 patients-257 males and 62 females (median age, 28 years)-with mandibular fractures (185 single, 116 double and 18 triple fractures) were hospitalised and treated with ORIF. Intraoperative MMF was performed manually on 112 (35%) patients and with rigid MMF on 207 (65%) patients. The study variables did not differ significantly between the two groups, except for age. Minor occlusion disturbances were observed in 4 (3.6%) patients in the manual MMF group and in 10 (4.8%) patients in the rigid MMF group (p > .05). In the rigid MMF group, only one case of major malocclusion required a revision surgery. Infective complications involved 3.6% and 5.8% of patients in the manual and rigid MMF group, respectively (p > .05). CONCLUSION: Intraoperative MMF was performed manually in nearly one third of the patients, with wide variability among the centres and no difference observed in terms of number, site and displacement of fractures. No significant difference was found in terms of postoperative malocclusion among patients treated with manual or rigid MMF. This suggests that both techniques were equally effective in providing intraoperative MMF.

Sensitivity and specificity of chest ultrasound in the diagnosis of pulmonary embolism in the emergency department: A case-control study.

Objectives: The present study was designed to evaluate the role of chest ultrasound in the diagnosis of acute pulmonary embolism (PE) and determine its accuracy using multi-detector CT-pulmonary angiography (MD-CTPA) as a gold standard technique for PE diagnosis. Patients and methods: A prospective case-control study was performed with 75 patients who presented to the emergency department of Minia Cardiothoracic University Hospital with clinical suspicion of PE. All patients were evaluated clinically and by laboratory tests to assess the risk of PE. Thoracic ultrasound (TUS) was then performed for all patients for signs suggestive of PE. Finally, MD-CTPA was performed to confirm or exclude the presence of PE. Results: Patients were subdivided into two groups according to the result of MD-CTPA; group I (patients with PE) and group II (control group without PE). In our study, PE was present in the lower lobe in 75% of cases, then in the middle in 13% and in the upper lobe in 3.8% of cases. The majority of lesions in TUS were wedge-shaped lesions. No vascular flow was detected in 83% of PE-confirmed patients. The current study revealed that TUS has 81.25% sensitivity, 95% specificity, 98.3% positive predictive value, 77.2% negative predictive value and 87% accuracy in the diagnosis of PE. Univariate regression analysis revealed that the presence of wedge-shaped pleural-based lesions in grayscale US and the absence of flow signals by colour Doppler sonography (CDS) increase the possibility of PE. Wedge-shaped pleural-based lesions increase the possibility of PE by 1.48 times (P=0.0001), and the absence of flow signals by CDS increases the possibility of PE by 92.89 times (P=0.00001). Multivariate regression analysis revealed that adding absent flow signals by CDS to wedge-shaped pleural-based lesions by grayscale US increases the possibility of a PE diagnosis by 50.28 times (P=0.001). Conclusion: Chest ultrasound is a simple, safe, noninvasive, inexpensive, bedside diagnostic radiological technique that can be used in the emergency department for suspected PE or as an alternative to MD-CTPA when CTPA is contraindicated. Wedge-shaped lesions and the absence of flow signals by CDS increase the diagnostic value of ultrasound for PE.

Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats.

Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent.

Extracellular ATP targets Arabidopsis RIBONUCLEASE 1 to suppress mycotoxin stress-induced cell death.

Extracellular ATP is a purinergic signal with important functions in regulating plant growth and stress-adaptive responses, including programmed cell death. While signalling events proximate to receptor activation at the plasma membrane have been characterised, downstream protein targets and the mechanism of cell death activation/regulation are unknown. We designed a proteomic screen to identify ATP-responsive proteins in Arabidopsis cell cultures exposed to mycotoxin stress via fumonisin B1 (FB1) application. Arabidopsis RIBONUCLEASE 1 (RNS1) was identified by the screen, and transgenic plants overexpressing native RNS1 showed greater susceptibility to FB1, while a gene knockout rns1 mutant and antisense RNS1 transgenic plants were resistant to FB1-induced cell death. Native RNS1 complemented rns1 mutants and restored the cell death response to FB1, while a catalytically inactive version of the ribonuclease could not. The FB1 resistance of salicylic acid (SA)-depleted nahG-expressing plants was abolished by transformation with native RNS1, but not the catalytically dead version. The mechanism of FB1-induced cell death is activation of RNS1-dependent RNA cleavage, which is blocked by ATP via RNS1 suppression, or enhanced by SA through induction of RNS1 expression. Our study reveals RNS1 as a previously unknown convergence point of ATP and SA signalling in the regulation of stress-induced cell death.

A low-cost, portable, and practical LAMP device for point-of-diagnosis in the field.

Transition of rapid, ready-to-use, and low-cost nucleic acid-based detection technologies from laboratories to points of sample collection has drastically accelerated. However, most of these approaches are still incapable of diagnosis starting from sampling through nucleic acid isolation and detection in the field. Here we developed a simple, portable, low-cost, colorimetric, and remotely controllable platform for reliable, high-throughput, and rapid diagnosis using loop-mediated isothermal amplification (LAMP) assays. It consists of a thermally isolated cup, low-cost electronic components, a polydimethylsiloxane sample well, and a fast prototyped case that covers electronic components. The steady-state temperature error of the system is <1%. We performed LAMP, Colony-LAMP, and Colony polymerase chain reactions (PCRs) using the yaiO2 primer set for Escherichia coli and Pseudomonas aeruginosa samples at 65°C and 30 min. We detected the end-point colorimetric readouts by the naked eye under day light. We confirmed the specificity and sensitivity of our approach using pure genomic DNA and crude bacterial colonies. We benchmarked our Colony-LAMP detection against Colony PCR. The number of samples tested can easily be modified for higher throughput in our system. We strongly believe that our platform can greatly contribute rapid and reliable diagnosis in versatile operational environments.

Factors associated with weight loss in people with overweight or obesity living with type 2 diabetes mellitus: Insights from the global DISCOVER study.

AIMS: To estimate real-world change in weight over 3 years and the factors influencing it in participants who are overweight and live with type 2 diabetes. MATERIALS AND METHODS: DISCOVER is a multinational prospective observational study that enrolled participants with type 2 diabetes between December 2014 and June 2016 at the time of initiation of a second-line glucose-lowering medication (GLM). Demographic, anthropometric, and quality-of-life data were collected at baseline, and after 6, 12, 24 and 36 months of follow-up. Using a hierarchical, repeated-measures linear regression model, we examined factors associated with weight change over time. RESULTS: Of 10 675 participants with type 2 diabetes who were overweight/obese (mean age 57.1 ± 11.1 years, 46% women), 21% lost ≥5% weight over 3 years, which was associated with modestly improved physical and mental health. Advancing age, female sex, and higher baseline weight were associated with weight loss. Most importantly, the type of GLM prescribed at previous visit had the strongest impact on weight change over time independent of participant factors, with use of a sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist associated with 1.0% weight loss versus a 0.6% weight gain with sulphonylureas, thiazolidinediones, meglitinides or insulin. CONCLUSION: In this large contemporary prospective study, approximately one in five participants with early-stage type 2 diabetes and overweight/obesity lost ≥5% weight over 3 years. The type of GLM has the most impact on weight loss over time, highlighting the need for a careful selection of agents that takes baseline weight into consideration.

Deprotonation of phenol linked to a silicon dioxide surface using adaptive feedback laser control with a heterodyne detected sum frequency generation signal.

The development of laser-controlled surface reactions has been limited by the lack of decisive methods for detecting evolving changes in surface chemistry. In this work, we demonstrate successful laser control of a surface reaction by combining the adaptive feedback control (AFC) technique with surface sensitive spectroscopy to determine the optimally shaped laser pulse. Specifically, we demonstrate laser induced deprotonation of the hydroxyl group of phenol bound to a silicon dioxide substrate. The experiment utilized AFC with heterodyne detected vibrational sum frequency generation (HD-VSFG) as the surface sensitive feedback signal. The versatile combination of AFC with HD-VSFG provides a route to potentially control a wide range of surface reactions.

An Investigation of The Effect of Extracellular Vesicles Isolated from Mouse Embryonic Fibroblasts on Wound Healing in an Experimental Diabetic Mouse Model.

This study aimed to investigate the effects of Extracellular Vesicles (EV) secreted from mouse embryonic fibroblasts EV on wound healing of full-thickness skin defect in a diabetic mouse model. The study included both in vitro and in vivo experimental studies 82 mice. In the in vitro stage of the experimental study, hysterectomy was performed on two mice between the 13-14th days of pregnancy and then EV was isolated by cell culturing. VEGF, IL-6, and TNF-α biomarkers were examined in tissue homogenate. Moreover, tissue taken from wound area was also subjected to histopathologic scoring. EV augmented the effect of VEGF. Therefore promoted angiogenesis increases the transport of cells, essential oxygen and nutrients in the wound area. Extracellular vesicles isolated from mouse embryonic fibroblasts have been found to accelerate wound healing in diabetes. The findings obtained from this experimental study indicate that EV isolated from mouse embryonic fibroblasts accelerate the wound healing process in experimentally induced-diabetes in mice.

Patient-centered contrast thresholds to reduce acute kidney injury in high-risk patients undergoing percutaneous coronary intervention.

BACKGROUND: Contrast volume used during percutaneous coronary intervention has a direct relationship with contrast-associated acute kidney injury. While several models estimate the risk of contrast-associated acute kidney injury, only the strategy of limiting contrast volume to 3 × estimated glomerular filtration rate (eGFR) gives actionable estimates of safe contrast volume doses. However, this method does not consider other patient characteristics associated with risk, such as age, diabetes or heart failure. METHODS: Using the National Cardiovascular Data Registry acute kidney injury risk model, we developed a novel strategy to define safe contrast limits by entering a contrast term into the model and using it to meet specific (eg, 10%) relative risk reductions. We then estimated acute kidney injury rates when our patient-centered model-derived thresholds were and were not exceeded using data from CathPCI version 5 between April 2018 and June 2019. We repeated the same analysis in a sub-set of patients who received ≤3 × eGFR contrast. RESULTS: After excluding patients on hemodialysis, below average risk (<7%), missing data and multiple percutaneous coronary interventions, our final analytical cohort included 141,133 patients at high risk for acute kidney injury. The rate of acute kidney injury was 10.0% when the contrast thresholds derived from our patient-centered model were met and 18.2% when they were exceeded (P < .001). In patients who received contrast ≤3 × eGFR (n = 82,318), contrast-associated acute kidney injury rate was 9.8% when the contrast thresholds derived from our patient centered model were met and 14.5% when they were exceeded (P < .001). CONCLUSIONS: A novel strategy for developing personalized contrast volume thresholds, provides actionable information for providers that could decrease rates of contrast-associated acute kidney injury. This strategy needs further prospective testing to assess efficacy in improving patient outcomes.

Patterns of care and dropout rates from outpatient mental healthcare in low-, middle- and high-income countries from the World Health Organization's World Mental Health Survey Initiative.

BACKGROUND: There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries. METHODS: Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan-Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function. RESULTS: Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care. CONCLUSIONS: Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.

Basis of Image Analysis for Evaluating Cell Biomaterial Interaction Using Brightfield Microscopy.

Medical imaging is a growing field that has stemmed from the need to conduct noninvasive diagnosis, monitoring, and analysis of biological systems. With the developments and advances in the medical field and the new techniques that are used in the intervention of diseases, very soon the prevalence of implanted biomedical devices will be even more significant. The implanted materials in a biological system are used in diverse fields, which require lengthy evaluation and validation processes. However, currently the evaluation of the toxicity of biomaterials has not been fully automated yet. Moreover, image analysis is an integral part of biomaterial research, but it is not within the core capacities of a significant portion of biomaterial scientists, which results in the use of predominantly ready-made tools. The detailed image analysis can be conducted once all the relevant parameters including the inherent characteristics of image acquisition techniques are considered. Herein, we cover the currently used image analysis-based techniques for assessment of biomaterial/cell interaction with a specific focus on unstained brightfield microscopy acquired mostly in but not limited to microfluidic systems, which serve as multiparametric sensing platforms for noninvasive experimental measurements. We present the major imaging acquisition techniques that enable point-of-care testing when incorporated with microfluidic cells, discuss the constraints enforced by the geometry of the system and the material that is analyzed, and the challenges that rise in the image analysis when unstained cell imaging is employed. Emerging techniques such as utilization of machine learning and cell-specific pattern recognition algorithms and potential future directions are discussed. Automation and optimization of biomaterial assessment can facilitate the discovery of novel biomaterials together with making the validation of biomedical innovations cheaper and faster.