Association of anxiolytic drugs with Torsade de Pointes: a pharmacovigilance study of the Food and Drug Administration Adverse Event Reporting System.

Background: This study aimed to determine the association of Torsade de Pointes (TdP) with anxiolytic drugs and present a detailed overview of anxiolytic-induced cases of TdP reported to the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: All cases of anxiolytic-induced TdP (n = 260) between 1990 and 2020 were retrieved from the FAERS database using the Preferred Term 'Torsade de Pointes, code: 10044066' from the Medical Dictionary for Regulatory Activities (MedDRA version 22). Four data-mining algorithms were used for disproportionality analysis: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Information Content (IC). Anxiolytics with ≥3 TdP cases were included. Results: Of a total of eight drugs, this study identified seven signals of TdP, of which six signals were new, namely for alprazolam, bromazepam, lorazepam, meprobamate, midazolam, and oxazepam. Based on disproportionality analysis, among new signals, the highest risk of TdP was observed with bromazepam and midazolam. Alprazolam showed the lowest risk for TdP, while diazepam did not reach significant disproportionality. Conclusions: This study identified six new signals of TdP among anxiolytic drugs, so warranting stringent clinical studies to ascertain the actual risk of TdP and ensure patient safety. Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT.gov ID: NCT04293432).

A Comparative Study on the Safety and Efficacy of Erbium Laser Therapy Versus Traditional Treatments in Managing Dentin Hypersensitivity: An Observational Study.

Background This study aimed to explore the potential efficacy and safety of laser therapy compared with traditional desensitizing treatments in the management of dentin hypersensitivity. Methodology A comprehensive observational study was conducted on 138 adult individuals aged 18-65 diagnosed with dentin hypersensitivity. Participants were allocated to either the laser therapy or traditional treatment group. The laser therapy group received treatment using the Fotona LightWalker® Erbium laser at 2,940 nm. The energy density was set at 20 J/cm² using continuous and contact modes, with the laser tip held perpendicularly to the irradiated site. Each session lasted five minutes, conducted bi-weekly for three months. Traditional treatment included the in-office application of 5% sodium fluoride varnish application once every 15 days for three months and the use of desensitizing toothpaste as part of regular oral hygiene routines. Follow-up assessments were conducted 6 and 12 months post-treatment to evaluate the longevity and stability of the treatment effects. Primary outcomes were assessed by dentin hypersensitivity reduction measured using Visual Analog Scale (VAS) scores and tactile hypersensitivity assessments. Results Laser therapy consistently surpassed traditional treatment in reducing dentin hypersensitivity, as reflected by the significantly lower VAS scores. Notably, at 3, 6, and 12 months, laser therapy demonstrated mean VAS scores of 2.5 (±1.5), 1.2 (±0.9), and 0.6 (±0.5), respectively, while the traditional treatment group exhibited higher scores (3.8 ± 1.2, 4.5 ± 1.0, and 4.0 ± 0.7, respectively). Statistical analysis revealed that these differences were highly significant (p < 0.001). Tactile hypersensitivity assessments echoed these findings, with laser therapy consistently maintaining lower scores (0.8 ± 0.7 at 6 months, 0.4 ± 0.3 at 12 months) compared to traditional treatment (3.5 ± 1.0 at 6 months, 4.0 ± 0.7 at 12 months) with statistical significance at all time points (p < 0.001). Conclusions Although this study lacks a randomized controlled design, the observed substantial reduction in VAS scores and tactile hypersensitivity assessments, along with the favorable safety profile of laser therapy, suggest its potential as an effective alternative for managing dentin hypersensitivity.

A potential toxicological risk assessment of heavy metals and pesticides in irrigated rice cultivars near industrial areas of Dhaka, Bangladesh.

Rice intake represents a significant pathway through which humans accumulate heavy metals. This study presents a comprehensive analysis of heavy metal and pesticide contamination in rice cultivars irrigated with industrial wastewater near Dhaka, Bangladesh, a region heavily influenced by industrial activities. This study employed a unique methodology that not only quantified the concentrations of heavy metals and pesticide residues in rice grains but also extended to evaluating the physicochemical properties of rice stems, husks, soil, and irrigation water. The findings revealed alarmingly high levels of heavy metals such as lead, cadmium, chromium, nickel, and mercury in the soil and irrigation water, with concentrations in some cases exceeding the World Health Organization safety thresholds by 2 to 15 times. Notably, the rice grains also exhibited significant contamination, including substantial amounts of diazinon and fenitrothion pesticides, exceeding the established safety limits. The study employed hazard quotients (HQs) and cancer risk (CR) assessments to evaluate the potential health risks associated with the consumption of contaminated rice. The results indicated HQ values were greater than 1 for rice grains across the sampled fields, suggesting a considerable non-carcinogenic health risk, particularly from lead exposure, which was found at levels twice the standard limit in all the sampling fields. Moreover, the CR values for As, Pb, Cd, Co, and Mn highlighted a significant carcinogenic risk in several instances.

Neuroprotective effect of diosmin against chlorpyrifos-induced brain intoxication was mediated by regulating PPAR-γ and NF-κB/AP-1 signals.

Chlorpyrifos (CPF) is a widely used organophosphate (OP) pesticide. Unfortunately, pesticides are known to cause neuronal intoxication. Diosmin (DS) is an antioxidant, anti-inflammatory, and neuroprotective flavonoid with high efficacy and safety. We plan to investigate the efficacy of DS in treating CPF-induced neurotoxicity, as well as the mechanisms underlying the protective effects. In our study, rats were randomized into 5 groups: control, DS (50 mg/kg), CPF (10 mg/kg), CPF + DS (25 mg/kg), and CPF + DS (50 mg/kg). The results indicated that DS ameliorated neuronal intoxication induced by CPF, evidenced by decreasing Tau, p-Tau, and ß-amyloid. Histological examinations support these findings. DS significantly ameliorated CPF-induced neuronal oxidative injury by decreasing MDA content and elevating GSH, GST, and SOD levels mediated by PPAR-γ upregulation. DS suppressed CPF-induced brain inflammation by decreasing MPO enzymatic activity and TNF-α, IL-1ß, and IL-6 levels mediated by downregulation of NF-κB/AP-1(c-FOS and c-JUN) signal. Of note, DS protective effects were dose dependent. In conclusion, our data suggested that DS was a promising therapeutic strategy for attenuating CPF-induced neuronal intoxication by restoring oxidant-antioxidant balance and inhibiting inflammatory response in brain tissues.

Heparin-Induced Hemorrhagic Bullous Dermatosis: A Rare Complication of Unfractionated Heparin.

We present a case of an 82-year-old female with a significant medical history of hypertension and Alzheimer's disease who developed heparin-induced hemorrhagic bullous dermatosis during treatment for a subsegmental pulmonary embolism. The patient was admitted with lower extremity edema and cyanosis, diagnosed with a subsegmental pulmonary embolism, and started on therapeutic doses of unfractionated heparin. On the sixth day of heparin therapy, she developed abdominal bloating and a diffuse exanthematous rash, which progressed to hemorrhagic bullae on the plantar and dorsal aspects of her feet, alongside extensive purpura on her legs. Laboratory findings revealed thrombocytopenia. Multidisciplinary consultations confirmed the diagnosis of heparin-induced hemorrhagic bullous dermatosis. Management included continuing unfractionated heparin with close monitoring, supportive topical treatments, and a subsequent transition to rivaroxaban. The patient's condition improved significantly, and she was discharged in stable condition. This case highlights the importance of recognizing rare adverse reactions to heparin and raises the question of preventive measures or risk factors related to this manifestation.

Chitosan based ethanolicAllium Sativumextract hydrogel film: a novel skin tissue regeneration platform for 2nd degree burn wound healing.

This study investigated the potential of ethanolic garlic extract-loaded chitosan hydrogel film for burn wound healing in an animal model. The ethanolic garlic extract was prepared by macerating fresh ground garlic cloves in ethanol for 24 h, followed by filtration and concentration using a rotary evaporator. Hydrogels were then prepared by casting a chitosan solution with garlic extract added at varying concentrations for optimization and, following drying, subjected to various characterization tests, including moisture adsorption (MA), water vapor transmission rate (WVTR), and water vapor permeability rate (WVPR), erosion, swelling, tensile strength, vibrational, and thermal analysis, and surface morphology. The optimized hydrogel (G2) was then analyzedin vivofor its potential for healing 2nd degree burn wounds in rats, and histological examination of skin samples on day 14 of the healing period. Results showed optimized hydrogel (G2; chitosan: 2 g, garlic extract: 1 g) had MA of 56.8% ± 2.7%, WVTR and WVPR of 0.00074 ± 0.0002, and 0.000 498 946 ± 0.0001, eroded up to 11.3% ± 0.05%, 80.7% ± 0.04% of swelling index, and tensile strength of 16.6 ± 0.9 MPa, which could be attributed to the formation of additional linkages between formulation ingredients and garlic extract constituents at OH/NH and C=O, translating into an increase in transition melting temperature and enthalpy (ΔT= 238.83 °C ± 1.2 °C, ΔH= 4.95 ± 0.8 J g-1) of the chitosan moieties compared with blank. Animal testing revealed G2 formulation significantly reduced the wound size within 14 d of the experiment (37.3 ± 6.8-187.5 ± 21.5 mm2) and had significantly higher reepithelization (86.3 ± 6.8-26.8 ± 21.5 and 38.2% ± 15.3%) compared to untreated and blank groups by hastening uniform and compact deposition of collagen fibers at the wound site, cementing developed formulation a promising platform for skin regeneration.

Correction: Ben Ammar et al. Anti-Inflammatory Activity of Geraniol Isolated from Lemon Grass on Ox-LDL-Stimulated Endothelial Cells by Upregulation of Heme Oxygenase-1 via PI3K/Akt and Nrf-2 Signaling Pathways. Nutrients 2022, 14, 4817.

In the original publication [...].

Therapy-induced senescent cancer cells exhibit complement activation and increased complement regulatory protein expression.

Therapy-induced senescence (TIS) is a primary response to chemotherapy, contributing to untoward treatment outcomes such as evasion of immunosurveillance. Despite the established role of the complement system in the immune response to cancer, the role of complement in mediating the immune response against senescent tumor cells remains poorly understood. To explore this relationship, we exposed lung adenocarcinoma (A549), breast adenocarcinoma (MCF7) and pancreatic carcinoma (Panc-1) cell lines to sublethal doses of either etoposide or doxorubicin to trigger TIS. Identification of TIS was based on morphological changes, upregulation of the senescence-associated ß-galactosidase, p21Cip1 induction and lamin B1 downregulation. Using immunofluorescence microscopy, quantitative PCR, ELISA of conditioned media and in silico analysis, we investigated complement activation, complement protein expression, C3 levels in the conditioned media of senescent cells and secreted complement proteins as part of the senescence-associated secretory phenotype (SASP), respectively. In cell lines undergoing TIS, complement-related changes included (i) activation of the terminal pathway, evidenced by the deposition of C5b-9 on senescent cells; (ii) an increase in the expression of CD59 and complement factor H and (iii) in A549 cells, an elevation in the expression of C3 with its secretion into the medium. In addition, increased C3 expression was observed in breast cancer samples expressing TIS hallmarks following exposure to neoadjuvant chemotherapy. In conclusion, TIS led to the activation of complement, upregulation of complement regulatory proteins and increased C3 expression. Complement appears to play a role in shaping the cancer microenvironment upon senescence induction.

Cisplatin Provokes Peripheral Nociception and Neuronal Features of Therapy-Induced Senescence and Calcium Dysregulation in Rats.

Therapy-Induced Senescence (TIS) is a form of senescence that is typically described in malignant cells in response to the exposure of cancer chemotherapy or radiation but can also be precipitated in non-malignant cells. TIS has been shown to contribute to the development of several cancer therapy-related adverse effects; however, evidence on its role in mediating chemotherapy-induced neurotoxicity, such as Chemotherapy-induced Peripheral Neuropathy (CIPN), is limited. We here show that cisplatin treatment over two cycles (cumulative dose of 23 mg/kg) provoked mechanical allodynia and thermal hyperalgesia in Sprague-Dawley rats. Isolation of dorsal root ganglia (DRG) from the cisplatin-treated rats demonstrated robust SA-ß-gal upregulation at both day 8 (after the first cycle) and day 18 (after the second cycle), decreased lmnb1 expression, increased expression of cdkn1a and cdkn2a, and of several factors of the Senescence-associated Secretory Phenotype (SASP) (Il6, Il1b, and mmp9). Moreover, single-cell calcium imaging of cultured DRGs revealed a significant increase in terms of the magnitude of KCl-evoked calcium responses in cisplatin-treated rats compared to vehicle-treated rats. No significant change was observed in terms of the magnitude of capsaicin-evoked calcium responses in cisplatin-treated rats compared to vehicle-treated rats but with decreased area under the curve of the responses in cisplatin-treated rats. Further evidence to support the contribution of TIS to therapy adverse effects is required but should encourage the use of senescence-modulating agents (senotherapeutics) as novel palliative approaches to mitigate chemotherapy-induced neurotoxicity.

A Prospective Observational Study of Preoperative Anaemia Management Aided by Bedside Haemoglobin Testers in a Low-Resource Setting.

AIM: Paediatric-preoperative anaemia management is challenging in settings where clinical judgment is used to diagnose anaemia owing to a lack of timely, affordable preoperative haemoglobin testing. We analysed anaemia management in such a setting after the introduction of point-of-care bedside haemoglobin testers. METHOD: 1033 children who underwent surgery at a hospital in Bangladesh were included in this study. 569 underwent major surgery, and 464 underwent minor surgery and belonged to predominantly ASA category 1 or 2. RESULTS: 940/1033 children underwent preoperative anaemia testing. Average haemoglobin was 11.7 g/dL. 103/1033 children were deemed clinically anaemic. However, 285 children were found to have anaemia based on bedside testing. Sensitivity of clinical judgement was 33.68% (95 % CI 28.22%-39.49%), and the specificity was 99.08% (95 % CI 98.02%-99.66%). 63/1033 had preoperative anaemia treatment, of whom 60 underwent transfusion. Subgroup analysis of children with haemoglobin <10 g/dL (n = 124) was done to compare conservative vs liberal transfusion strategy. 43/124 of this subset was transfused. Average length of stay for those transfused was 11.7 days, and those who weren't was 9.9 days (p = 0.087). 4 patients in the transfused subgroup required post-op ICU, and only 1 patient in the conservatively managed arm required ICU (p = 0.048). CONCLUSION: This study demonstrates the positive impact of bedside haemoglobin testers as they have resulted in a significantly higher proportion of children diagnosed with anaemia at a fraction of the cost and logistics involved in laboratory testing. Further research on haemoglobin thresholds is required to understand the safety and long-term impact of restrictive transfusion in the surgical context. LEVEL OF EVIDENCE: 2c (Grading as per the Oxford Centre for Evidence Based Medicine).

The Versatility of the Lateral-based Mammary Flap as an "Auto-implant" for Enhancing Breast Mound for Patients Undergoing Primary Mastopexy.

Background: The demand for augmentation-mastopexy surgery without using implants has significantly increased over the years. Fat transfer offers an alternative method, but some patients do not favor this procedure either. The purpose of this study was to evaluate the versatility of using a lateral-based mammary flap as an "auto-implant" for enhancing the breast mound for patients undergoing primary mastopexy. Method: This retrospective study was performed between February 2016 and April 2019, including 36 female patients (72 breasts). Our technique involves using the inferior breast tissue by elevating the lateral-based dermoglandular flap that was moved cranially with a 90 degree rotation in a conical shape within the created pocket to refill the superior and central mound. Result: The mean nipple projection was 11.2 after 36 months postoperative compared with 5.2 before surgery. The mean ± SD of pre- and postoperative measurements for the lower pole zone were 80.2 ± 10.5 and 50.1 ± 6.4, and those for the upper pole zone were 40.3 ± 9.5 and 63.9 ± 6.5, respectively. The distance of breast mound elevation after the surgical procedure ranged from 5.30 to 9.55 cm, with a mean of 7.90 cm. Conclusions: The lateral-based mammary flap acts like an implant that helps shape and augment the breast, enhances the mammary projection, and restores the breast contour without requiring a synthetic implant or fat grafting. It is a reliable technique with high patient satisfaction but is unsuitable for patients with insufficient breast volume.

A randomized controlled trial on the effect of smartphone-based mental health application among outpatients with depressive and anxiety symptoms: A pilot study in Malaysia.

Introduction: Despite the increasing number of mental health professionals in Malaysia, many have yet to receive adequate treatment for common mental illnesses such as depression and anxiety. Coupled with the increasing number of mobile phone users globally, smartphone-based intervention can be a promising mental health intervention. Thus, this study aims to investigate the efficacy of using a smartphone-based mental health application in addition to treatment-as-usual (TAU) in outpatients with depressive and/or anxiety symptoms. Methods: Psychiatric outpatients that fulfill the selection criteria were recruited and randomized into two groups, the intervention group (n = 24) and the control group (n = 24). Those in the intervention group received MoodMission in addition to TAU, while those in the control group received TAU. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scores were assessed at baseline and after four weeks. Results: A total of 48 participants were recruited, randomized, and completed the study. Baseline characteristics for both groups were comparable. There is no significant mean difference between-group comparison of PHQ-9 (1.31, 95% CI -1.35, 3.98) and GAD-7 (0.02, 95% CI -2.01, 2.05) scores at four weeks. However, for the intervention group, there was a significant improvement in the PHQ-9 score at four weeks [mean difference 2.58 (95% CI 1.16, 4.01), P = 0.001)]. Conclusion: This study showed no significant improvement in anxiety symptoms after four weeks. Use of smartphone-based mental health applications led to significant reduction of depressive symptoms.

Effects of Scaling and Root Planing on Salivary Interleukine-6 Levels in Chronic Periodontitis Patients and Glycemic Controls.

BACKGROUND:  Type 2 diabetes mellitus (DM) and periodontitis have a bidirectional relationship that is well documented in many reviews and epidemiological studies. Periodontitis has been referred to as the sixth complication of diabetes mellitus. Various studies showed improvement in Interleukin-6 levels as well as metabolic parameters after non-surgical periodontal therapy in chronic periodontitis patients with type 2 DM.  Objective: To evaluate the effect of scaling and root planing (SRP) on salivary levels of IL-6 and assessment of clinical parameters in CP patients with and without T2DM. METHODS: We included 50 CP patients with well-controlled T2DM (Group I), and 50 CP patients without T2DM as controls (Group II) with evident clinical inflammation, ≥ 5mm probing depth (PD) and a relative attachment level (RAL) of ≥ 5mm. Following a brief medical and dental history plaque index (PI), gingival index (GI), gingival bleeding index (BI), PD, and RAL were recorded, and an unstimulated saliva was collected. Following SRP therapy, the clinical parameters and IL-6 levels were measured after seven days, 14 days, and 30 days. Intragroup and intergroup comparisons were carried out using a paired t-test and an independent t-test. The statistical significance was set at P < 0.05. Data were analyzed using computer software, Statistical Package for Social Sciences (SPSS) v. 22.0 (IBM Corp., Armonk, NY). RESULTS: Intergroup comparisons of IL-6 levels at different intervals showed a significantly higher reduction in Group II than in Group I (p=0.000). While the mean difference in the GI scores from baseline to 30 days was significantly higher in Group I patients (p=0.000), the difference in the mean PI (p=0.004), mean BI (p=0.000), mean PD (p=0.000) and mean RAL scores (p=0.000) were significantly higher in Group II patients. CONCLUSION: This study indicates that scaling and root planing is effective in glycemic control and also has a role to play in the level of salivary IL-6 in periodontal health and T2DM with chronic periodontitis. Elevated salivary IL-6 levels indicate periodontal inflammation which is further increased in T2DM patients. Hence, elevated IL-6 can be considered a marker of periodontal destruction.

Bio-Stimulant for Improving Simmondsia chinensis Secondary Metabolite Production, as Well as Antimicrobial Activity and Wound Healing Abilities.

Simmondsia chinensis is a dioecious, long-lived perennial shrub. Its leaves contain several antioxidant flavonoids that have numerous pharmacological effects. Various strategies have been explored to propagate jojoba with enhanced pharmacological values. This research evaluates the bio-stimulatory impacts of He-Ne laser seed irradiation on seed germination, plantlet growth, and alteration of the composition and bioactivities of phytochemicals in jojoba plants. Jojoba seeds were irradiated for 5, 10, and 15 min before in vitro germination. Germination, growth, and multiplication parameters were recorded during germination, multiple-shoot induction, and rooting stages. The wound healing and antimicrobial activities of methanolic extracts from plant lines obtained from the non-irradiated (control) and 10 min irradiated seeds were compared by excision wound model in Wistar male rats and zone of inhibition assay. Our study revealed that laser irradiation increased seed germination, with the highest percentage observed in seeds irradiated for 10 min. Plant lines from the 10 min irradiated seeds produced more explants with higher explant heights and numbers of leaves, more roots, and higher photosynthetic pigment contents than those of control and other laser testings. By comparing plant extracts from the control and 10 min treatments, we observed that extracts from the 10 min treatment exhibited higher percentages of wound contraction and shorter epithelialization periods. In addition, these extracts also resulted in higher levels of angiogenesis elements (VEGF, TGF-ß1, and HIF-1α) and reduced the inflammation regulators (IL-1ß, IL-6, TNF-α, and NFκB) in the experimental rats. In concordance, extracts from the 10 min treatment also explained raised antibacterial activities towards Staphylococcus aureus and Escherichia coli. Our findings show that pre-sowing seed treatment with a He-Ne laser (632.8 nm) could be a good technique for stimulating S. chinensis plant growth and increasing the impact compound levels and biological activities.

NOXA expression is downregulated in human breast cancer undergoing incomplete pathological response and senescence after neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) is a frequently utilized approach to treat locally advanced breast cancer, but, unfortunately, a subset of tumors fails to undergo complete pathological response. Apoptosis and therapy-induced senescence (TIS) are both cell stress mechanisms but their exact role in mediating the pathological response to NAC is not fully elucidated. We investigated the change in expression of PAMIP1, the gene encoding for the pro-apoptotic protein, NOXA, following NAC in two breast cancer gene datasets, and the change in NOXA protein expression in response to NAC in 55 matched patient samples (pre- and post-NAC). PAMIP1 expression significantly declined in post-NAC in the two sets, and in our cohort, 75% of the samples exhibited a downregulation in NOXA post-NAC. Matched samples that showed a decline in NOXA post-NAC were examined for TIS based on a signature of downregulated expression of Lamin-B1 and Ki-67 and increased p16INK4a, and the majority exhibited a decrease in Lamin B1 (66%) and Ki-67 (80%), and increased p16INK4a (49%). Since our cohort consisted of patients that did not develop complete pathological response, such findings have clinical implications on the role of TIS and NOXA downregulation in mediating suboptimal responses to the currently established NAC.

Long-term clinical efficacy and safety of thalidomide in patients with transfusion-dependent ß-thalassemia: results from Thal-Thalido study.

Regular blood transfusion is the mainstay of treatment in transfusion-dependent ß-thalassemia (TDT); however, transfusions culminate in an array of serious complications. Therefore, a single-arm, non-randomized clinical trial was conducted in hydroxyurea refractory TDT patients to explore the long-term safety and efficacy of thalidomide. The primary outcomes for efficacy were rise in hemoglobin (Hb) level and changes in transfusion frequency. Whereas, several clinical and laboratory parameters were assessed for safety of thalidomide. Secondary outcomes included changes in serum ferritin, serum lactate dehydrogenase (LDH), serum uric acid, red blood cell indices, and size of liver and spleen. A total of 532 patients were followed for a period of 30 months. Significant increase in mean Hb level was identified at 6 months (1.4 g/dL, p ≤ 0.001) and 30 months (2 g/dL, p ≤ 0.001) in comparison with baseline. A total of 408 (76.7%) patients responded to thalidomide therapy (excellent responders 25.8%, good responders 31%, and partial responders 19.9%) and attained transfusion independence within 6 months of therapy. A significant decline in mean ferritin, LDH level, liver size, and spleen size was observed. No unfavorable effects were observed on kidney and liver functions. Mild adverse events were reported in 48 (9%) patients and serious adverse events, including cerebral vascular accident and portal vein thrombosis were reported in two patients each. This study concludes that thalidomide is an effective and well-tolerated drug that can improve Hb levels and reduce transfusion burden in hydroxyurea refractory TDT patients.Trial registration: This trial is registered at http://www.clinicaltrial.gov as # NCT03651102.

Increased burden of MDR bacterial infections; reflection from an antibiogram of ICUs of a tertiary care hospital.

INTRODUCTION: Infectious disease management in intensive care units (ICUs) is becoming more difficult due to increasing antimicrobial resistance. Hence, the aim of this study was to explore the nature of pathogens mostly encountered in an ICU and determine their antibiotic susceptibility through the compilation of ICU-specific antibiogram. METHODOLOGY: A descriptive cross-sectional study of the culture and sensitivity reports of ICU patients was conducted in a tertiary care hospital. An antibiogram was created according to the Clinical Laboratory Standards Institute (CLSI) M39-A4 guidelines. RESULTS: Of the total 597 reports, the most common specimen type were respiratory secretions (n = 174), followed by blood (n = 128), wounds (n = 108), and urine (n = 80). Out of 597 isolates, the most frequently isolated bacteria were Klebsiella species (n = 156), Pseudomonas aeruginosa (n = 117), Escherichia coli (n = 112), Enterobacter species (n = 56), Acinetobacter species (n = 52), Proteus species (n = 39), Staphylococcus aureus (n = 34) and coliform species (n = 31). An 84% multidrug resistance (MDR) rate was reported among the isolates studied, with Acinetobacter species being at the top with a 98% MDR rate. CONCLUSIONS: A substantial and alarming MDR rate was observed in our study. Furthermore, our findings demonstrated a potential interest in developing an ICU-specific antibiogram that is informative to clinicians in their clinical decision-making related to antibiotic therapy.

Three-dimensional cultures of gingival fibroblasts on fibrin-based scaffolds for gingival augmentation: A proof-of-concept study.

OBJECTIVE: Gingival tissue regeneration is associated with several challenges. Tissue engineering regenerates the different components of the tissues, providing three major elements: living cells, appropriate scaffolds, and tissue-inducing substances. This study aimed to regenerate the gingival connective tissue in vitro, using human gingival fibroblasts cultured in three-dimensional fibrin gel scaffolds. DESIGN: Human gingival fibroblasts were seeded in a novel three-dimensional fibrin gel scaffold and maintained in two media types: platelet lysate media (control) and collagen-stimulating media (test). Cellular viability and proliferation were assessed, and the production of collagen and other extracellular matrix components in these constructs was investigated and compared. RESULTS: Human gingival fibroblasts cultured in three-dimensional cultures were metabolically active and proliferated in both media. Furthermore, histologic sections, scanning electron microscopy, and quantitative polymerase chain reaction confirmed the production of higher levels of collagen and other extracellular matrix fibers in three-dimensional constructs cultured in collagen-stimulating media. CONCLUSIONS: Culturing human gingival fibroblasts in a novel three-dimensional fibrin gel scaffold containing collagen-stimulating media resulted in a tissue-equivalent construct that mimics human gingival connective tissue. The impact of these results should be considered for further investigations, which may help to develop a compatible scaffold for gingival soft tissue regeneration and treatment of mucogingival deformities.

Enhancement of the Desorption Properties of LiAlH4 by the Addition of LaCoO3.

The high hydrogen storage capacity (10.5 wt.%) and release of hydrogen at a moderate temperature make LiAlH4 an appealing material for hydrogen storage. However, LiAlH4 suffers from slow kinetics and irreversibility. Hence, LaCoO3 was selected as an additive to defeat the slow kinetics problems of LiAlH4. For the irreversibility part, it still required high pressure to absorb hydrogen. Thus, this study focused on the reduction of the onset desorption temperature and the quickening of the desorption kinetics of LiAlH4. Here, we report the different weight percentages of LaCoO3 mixed with LiAlH4 using the ball-milling method. Interestingly, the addition of 10 wt.% of LaCoO3 resulted in a decrease in the desorption temperature to 70 °C for the first stage and 156 °C for the second stage. In addition, at 90 °C, LiAlH4 + 10 wt.% LaCoO3 can desorb 3.37 wt.% of H2 in 80 min, which is 10 times faster than the unsubstituted samples. The activation energies values for this composite are greatly reduced to 71 kJ/mol for the first stages and 95 kJ/mol for the second stages compared to milled LiAlH4 (107 kJ/mol and 120 kJ/mol for the first two stages, respectively). The enhancement of hydrogen desorption kinetics of LiAlH4 is attributed to the in situ formation of AlCo and La or La-containing species in the presence of LaCoO3, which resulted in a reduction of the onset desorption temperature and activation energies of LiAlH4.

Isoimperatorin therapeutic effect against aluminum induced neurotoxicity in albino mice.

Background: Although aluminum (Al) is not biologically crucial to the human body, classical studies have demonstrated that excessive human exposure to Al can induce oxidative damage, neuroinflammatory conditions and neurotoxic manifestations implicated in Alzheimer's disease (AD). Exposure to Al was reported to be associated with oxidative damage, neuroinflammation, and to enhance progressive multiregional neurodegeneration in animal models. Several plant-derived natural biomolecules have been recently used to reduce the toxic effects of Al through decreasing the oxidative stress and the associated diseases. A good candidate still to be tested is an active natural furanocoumarin, the isoimperatorin (IMP) that can be extracted from Lemon and lime oils and other plants. Here, we examined the neuroprotective effects of IMP on aluminum chloride (AlCl3)-induced neurotoxicity in albino mice. Methods: Twenty-four male albino mice were used in this study. Mice were randomly devided into 5 groups. The first group was given distilled water as a control, the second group was given AlCl3 orally (10 mg/wt/day) starting from the 2nd week to the end of the 6th week, the third group received AlCl3 orally and IMP interperitoneally, i. p. (30 mg/wt/day) starting from week 2 till week 6 where IMP was supplement 1st and then 4 h later AlCl3 was given to mice. The fourth group received the control (IMP 30 mg/wt, i. p.) from the 2nd week till the end of the experiment. Rodent models of central nervous system (CNS) disorders were assessed using object location memory and Y-maze tests in 6th week began. Essential anti-inflammatory and oxidative stress indicators were evaluated, including interleukin-1 ß (IL-1ß), tumor necrosis factor α (TNF-α), malondialdehyde (MDA), total antioxidant capacity (TAC), and catalase activity (CAT). In addition, serum levels of brain neurotransmitters such as corticosterone, acetylcholine (ACh), dopamine and serotonin in brain homogenates were measured calorimetrically. Results: The study results revealed that the daily treatment of AlCl3 upregulated the TNF-α and IL-1ß levels, increased MDA accumulation, and decreased TAC and CAT activity. In addition, aluminum induced a reduction in concentrations of ACh, serotonin and dopamine in the brain. However, IMP significantly ameliorates the effect of AlCl3 through modulating the antioxidant and regulating the inflammatory response through targeting Nrf2 (NF-E2-related factor 2) and mitogen-activated protein kinase (MAPK). Conclusion: Thus, IMP might be a promising treatment option for neurotoxicity and neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, which are associated with neuro-inflammation and oxidative stress.