Mapping a sustainable approach: biosynthesis of lactobacilli-silver nanocomposites using whey-based medium for antimicrobial and bioactivity applications.

This study explores a sustainable approach for synthesizing silver nanocomposites (AgNCs) with enhanced antimicrobial and bioactivity using safe Lactobacillus strains and a whey-based medium (WBM). WBM effectively supported the growth of Lactobacillus delbrueckii and Lactobacillus acidophilus, triggering a stress response that led to AgNCs formation. The synthesized AgNCs were characterized using advanced spectroscopic and imaging techniques such as UV‒visible, Fourier transform infrared (FT-IR) spectroscopy, transmission electron (TEM), and scanning electron microscopy with energy dispersive X-ray analysis (SEM-Edx). Lb acidophilus-synthesized AgNCs in WBM (had DLS size average 817.2-974.3 ± PDI = 0.441 nm with an average of metal core size 13.32 ± 3.55 nm) exhibited significant antimicrobial activity against a broad spectrum of pathogens, including bacteria such as Escherichia coli (16.47 ± 2.19 nm), Bacillus cereus (15.31 ± 0.43 nm), Clostridium perfringens (25.95 ± 0.03 mm), Enterococcus faecalis (32.34 ± 0.07 mm), Listeria monocytogenes (23.33 ± 0.05 mm), methicillin-resistant Staphylococcus aureus (MRSA) (13.20 ± 1.76 mm), and filamentous fungi such as Aspergillus brasiliensis (33.46 ± 0.01 mm). In addition, Lb acidophilus-synthesized AgNCs in WBM exhibit remarkable free radical scavenging abilities, suggesting their potential as bioavailable antioxidants. These findings highlight the dual functionality of these biogenic AgNCs, making them promising candidates for applications in both medicine and nutrition.

Development of 1,5-diarylpyrazoles as EGFR/JNK-2 dual inhibitors: design, synthesis, moleecular docking, and bioactivity evaluation.

The eradication of multifactorial diseases, such as cancer, requires the design of drug candidates that attack multiple targets that contribute to the progression and proliferation of such diseases. Here, 1,5-diarylpyrazole derivatives bearing vanillin or sulfanilamide are developed as potential dual inhibitors of epidermal growth factor receptor (EGFR)/c-Jun N-terminal kinase 2 (JNK-2) for possible anticancer activity. These derivatives inhibited the growths of DLD-1, HeLa, K-562, SUIT-2 and HepG2 cancer cell lines, with minimum concentration required to inhibit half of the cellular growth (IC50) values of 2.7-63 µM. The tests confirmed that 5b and 5d were potent JNK-2 inhibitors, with IC50 of 2.0 and 0.9 µM, respectively, whereas 6 h selectively inhibited EGFR protein kinase (EGFR-PK) (IC50 = 1.7 µM). Notably, 6c inhibited both kinases, with IC50 values of 2.7 and 3.0 µM against EGFR-PK and JNK-2, respectively, offering a reference for designing mutual inhibitors of EGFR/JNK-2. The docking studies revealed the ability of the pyrazole ring to bind to the hinge region of the ATP binding site, thereby supporting the experimental inhibitory results. Furthermore, the developed compounds could induce apoptosis and induce cell cycle arrest at different cell phases.

CYP14 family in Caenorhabditis elegans: Mitochondrial function, detoxification, and lifespan.

CYP-14 members of the Caenorhabditis elegans (C. elegans) Cytochrome P450 (CYP) enzyme family, plays important roles in mitochondrial dysfunction, detoxification, lipid metabolism, defense and lifespan regulation. The review identifies CYP-14 members: cyp-14A1, cyp-14A2, cyp-14A3, cyp-14A4, cyp-14A5 and their homology with human CYP families. Despite limited studies on C. elegans cyp-14 members, the findings unraveled their complex crosstalk between mitochondrial stress, detoxification mechanisms, and lifespan regulation, emphasizing the complexity of these interconnected pathways as well as how their regulation depends on environmental cues changes including pH, nutrients, ROS and chemical stressors. The review underscores the translational relevance to human health, shedding light on potential human homologues and their implications in age-related, metabolic and respiratory diseases. Among other genes, cyp-14A2 and cyp-14A4 predominate the mitochondrial function, heat resistance, lipid metabolism, detoxification and lifespan pathways. In conclusion, these insights pave the way for future research, offering promising avenues for therapeutic interventions targeting CYP-14 activity to address age-related diseases and promote healthy aging.

A decade's overview of 2-aminothiophenes and their fused analogs as promising anticancer agents.

Over the past decades, cancer has been a challenging domain for medicinal chemists as it is an international health concern. In association, small molecules such as 2-aminothiophenes and their derivatives showed significant antitumor activity through variable modes of action. Therefore, this article aims to review the advances regarding these core scaffolds over the past 10 years, where 2-aminothiophenes and their fused analogs are classified and discussed according to their biological activity and mode of action, in the interest of boosting new design pathways for medicinal chemists to develop targeted antitumor candidates.

Flavipin from fungi as a potential inhibitor of rheumatoid arthritis signaling molecules.

Flavipin, a fungal lower molecular weight biomolecule (MW 196.16 g/mol), has not been yet extensively studied for beneficial preclinical and clinical applications. In recent years, various preclinical mouse models including adjuvant-induced arthritis (AIA) were employed to understand mechanisms associated with Rheumatoid arthritis (RA) and to develop new therapeutic drugs. In the current study, we studied the inhibitory effect of Flavipin on major signaling molecules involved in the inflammatory response during RA using both in-silico virtual interaction and in vivo mouse model of AIA. Our in-silico results clarified that Flavipin interacts with the tumor necrosis factor alpha (TNF-α) through conventional hydrogen binding (H-H) at one of TNF-α critical amino acids tyrosine residues, Tyr119, with binding energy (b.e.) -5.9. In addition, Flavipin binds to ATP-binging sites of the Jesus kinases, JAK1, JAK2 and JAK3, through H-H (b. e. between -5.8 and -6.1) and then it may inhibit JAKs, regulators of RA signaling molecules. Moreover, our molecular dynamics stimulation for the docked TNF-α/Flavipin complex confirmed the specificity and the stability of the interaction. In vitro, Flavipin is not toxic to normal cells at doses below 50 µM (its IC50 in normal fibroblast cell line was above 100 µM). However, in vivo, the arthritis score and hind paw oedema parameters were modulated in Flavipin treated mice. Consistent with the in-silico results the levels of the TNF-α, the nuclear transcription factor kappaB (NF-κB) and the signal transduction and activator of transcription (STAT3, downstream of JAKs) were modulated at joint tissues of the hind-paw of Flavipin/AIA treated mice. Our data suggest Flavipin as a potential therapeutic agent for arthritis can inhibit RA major signaling molecules.

Evaluation of Quality of Life and Satisfaction with Fixed Prostheses on Zygomatic Implants vs All-on-Four Concept: A Randomized Clinical Study.

AIM: To compare between the rehabilitation of atrophied maxilla with fixed prosthesis using two posterior zygomatic implants and two conventional anterior implants or four implants inserted according to the all-on-four concept regarding the patient quality of life and satisfaction after one year of prosthesis insertion. MATERIALS AND METHODS: Thirty-six patients with atrophic edentulous maxillae were randomized into two groups: Group I (rehabilitated with fixed prostheses supported by two zygomatic and two conventional implants in the anterior region) and group II (fixed prostheses on four implants in the anterior region following an all-on-four concept). One year after the placement of the definitive prostheses, patients completed oral health impact profile-14 and satisfaction questionnaires. RESULTS: All patients were satisfied regarding retention, stability, occlusion, comfort, cleaning, speaking, chewing, bolus quality, appearance, handling, prosthesis apart, and embarrassing, with no significant significance between two groups except satisfaction with surgical procedures and healing period. CONCLUSIONS: Using two distally tilted zygomatic implants or all-on-four concept to rehabilitate atrophied maxilla by fixed detachable prosthesis could be considered a promising functional and esthetic treatment option regarding the patient satisfaction. CLINICAL SIGNIFICANCE: Traditionally, treatment of maxillary atrophied ridges was done by bone grafting or sinus-lifting techniques; however, using all-on-four concept or zygomatic implants was a successful treatment as it has high success rates and highly satisfied by the patients. How to cite this article: Nagib MA, Ibrahim AM, Abdel-Rahman FH, et al. Evaluation of Quality of Life and Satisfaction with Fixed Prostheses on Zygomatic Implants vs All-on-Four Concept: A Randomized Clinical Study. J Contemp Dent Pract 2024;25(2):141-147.

Interstitial cells of Cajal - pacemakers of the gastrointestinal tract.

Gastrointestinal (GI) organs display spontaneous, non-neurogenic electrical, and mechanical rhythmicity that underlies fundamental motility patterns, such as peristalsis and segmentation. Electrical rhythmicity (aka slow waves) results from pacemaker activity generated by interstitial cells of Cajal (ICC). ICC express a unique set of ionic conductances and Ca2+ handling mechanisms that generate and actively propagate slow waves. GI smooth muscle cells lack these conductances. Slow waves propagate actively within ICC networks and conduct electrotonically to smooth muscle cells via gap junctions. Slow waves depolarize smooth muscle cells and activate voltage-dependent Ca2+ channels (predominantly CaV1.2), causing Ca2+ influx and excitation-contraction coupling. The main conductances responsible for pacemaker activity in ICC are ANO1, a Ca2+ -activated Cl- conductance, and CaV3.2. The pacemaker cycle, as currently understood, begins with spontaneous, localized Ca2+ release events in ICC that activate spontaneous transient inward currents due to activation of ANO1 channels. Depolarization activates CaV 3.2 channels, causing the upstroke depolarization phase of slow waves. The upstroke is transient and followed by a long-duration plateau phase that can last for several seconds. The plateau phase results from Ca2+ -induced Ca2+ release and a temporal cluster of localized Ca2+ transients in ICC that sustains activation of ANO1 channels and clamps membrane potential near the equilibrium potential for Cl- ions. The plateau phase ends, and repolarization occurs, when Ca2+ stores are depleted, Ca2+ release ceases and ANO1 channels deactivate. This review summarizes key mechanisms responsible for electrical rhythmicity in gastrointestinal organs.

The effect of piezoelectric shockwave lithotripsy with 2- and 8-mm focus sizes on stone disintegration and renal injury.

OBJECTIVES: To compare the efficacy and safety of shockwave lithotripsy (SWL) using a narrow focus or wide focus for renal stones. PATIENTS AND METHODS: A double-blind randomised trial included adult patients with a solitary radio-opaque renal pelvic stone of 1-2 cm. Patients were randomised into two groups: narrow-focus (2 mm) SWL and wide-focus (8 mm) SWL. The stone-free rate (SFR) and presence of complications such as haematuria, fever, pain, and peri-renal haematoma were evaluated. Pre- and postoperative urinary markers (neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule 1 [KIM-1]) concentrations were compared to assess renal injury. RESULTS: A total of 135 patients were recruited for this study. The SFR after the first SWL session was 79.2% and 69.1% in narrow- and wide-focus groups, respectively. There was a comparable rise in the median 2-h NGAL concentration in both groups (P = 0.62). However, the rise in the median (interquartile range [IQR]) 2-h KIM-1 concentration was significantly higher in the narrow-focus group at 4.9 (4.6, 5.8) ng/mL compared with the wide-focus group at 4.4 (3.2, 5.7) ng/mL (P = 0.02). Nevertheless, the 3-day NGAL and KIM-1 urinary marker concentrations were significantly improved (P = 0.263 and P = 0.963, respectively). The overall SFR after three sessions was 86.6% and 86.8% in the narrow- and wide-focus groups, respectively (P = 0.77). Both groups were comparable for complications, apart from the median pain score and the percentage of high-grade haematuria, which were significantly higher in the narrow-focus group (P < 0.001 and P = 0.03, respectively). CONCLUSION: Narrow- and wide-focus SWL were associated with comparable outcomes and re-treatment rates. However, narrow-focus SWL was associated with significantly higher morbidity in terms of pain and haematuria.

Evaluation and comparison of retention and patient satisfaction with milled polyetheretherketone versus metal maxillary obturators.

STATEMENT OF PROBLEM: Metal and polyetheretherketone (PEEK) have been used to rehabilitate maxillary defects with obturators, each having advantages and disadvantages. However, patient satisfaction with the obturator retention of each material is unclear. PURPOSE: The purpose of this crossover clinical study was to compare retention and patient satisfaction between a milled cobalt chromium and a milled PEEK framework, each with a hollow bulb extension in polymethyl methacrylate (PMMA). MATERIAL AND METHODS: Twenty patients who had received unilateral total maxillectomy and were treated in the prosthodontic department's maxillofacial clinic were enrolled in this crossover study. Each participant wore 2 different types of obturators for 6 months after insertion. Type CoCr received a milled cobalt chromium framework with a hollow bulb extension in PMMA first, and type Pk received a milled modified PEEK (BioHPP) framework with a hollow bulb extension in PMMA first. Patient satisfaction and retention force were measured immediately, at 3 months, and at 6 months after obturator insertions. The Fischer exact, chi-squared, and Monte Carlo tests were used to compare qualitative data. One-way ANOVA with the post hoc Tukey test was used for pair-wise comparison, and repeated measures ANOVA was used to compare before and after treatment at 3 and 6 months. RESULTS: No significant difference was found between types in obturator insertion (P>.999), appearance of the upper lip (P>.999), mouth feeling (P=.301), pronunciation of words (P=.217), and talking in public (P=.589). A significant difference between types was found in speech after 6 months of obturator insertion (P=.016), swallowing liquids and food (P=.04), masticating foods (P=.007), appearance of clasps on anterior teeth (P=.002), satisfaction with appearance (P=.005), or avoidance of family events (P=.014) after 6 months of insertion. Types of obturators showed a statistically significant decrease in retention force with time (P<.001). CONCLUSIONS: Although the retention force was less with PEEK than with Co-Cr clasps engaging the same undercuts, this retention force was adequate for retaining removable partial dentures. Co-Cr clasps can be considered better than PEEK clasps because they engage the same undercuts regarding loss of retention with time. Quality of life in patients after maxillary resection could be improved by using maxillary obturators. Type Pk was better than type CoCr in terms of esthetics, but the retention of the PEEK obturator after 6 months decreased because of wear, leading to difficulty swallowing food or liquids, mastication, and speech.

Development and Assessment of 1,5-Diarylpyrazole/Oxime Hybrids Targeting EGFR and JNK-2 as Antiproliferative Agents: A Comprehensive Study through Synthesis, Molecular Docking, and Evaluation.

New 1,5-diarylpyrazole oxime hybrid derivatives (scaffolds A and B) were designed, synthesized, and then their purity was verified using a variety of spectroscopic methods. A panel of five cancer cell lines known to express EGFR and JNK-2, including human colorectal adenocarcinoma cell line DLD-1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cell line SUIT-2, and human hepatocellular carcinoma cell line HepG2, were used to biologically evaluate for their in vitro cytotoxicity for all the synthesized compounds 7a-j, 8a-j, 9a-c, and 10a-c. The oxime containing compounds 8a-j and 10a-c were more active as antiproliferative agents than their non-oxime congeners 7a-j and 9a-c. Compounds 8d, 8g, 8i, and 10c inhibited EGFR with IC50 values ranging from 8 to 21 µM when compared with sorafenib. Compound 8i inhibited JNK-2 as effectively as sorafenib, with an IC50 of 1.0 µM. Furthermore, compound 8g showed cell cycle arrest at the G2/M phase in the cell cycle analysis of the Hela cell line, whereas compound 8i showed combined S phase and G2 phase arrest. According to docking studies, oxime hybrid compounds 8d, 8g, 8i, and 10c exhibited binding free energies ranging from -12.98 to 32.30 kcal/mol at the EGFR binding site whereas compounds 8d and 8i had binding free energies ranging from -9.16 to -12.00 kcal/mol at the JNK-2 binding site.

Polyetheretherketone computer-aided design and computer-aided manufacturing framework for All-on-Four mandibular full-arch prosthesis: 3 Years' retrospective study of peri-implant soft tissue changes and ridge base relationship.

PURPOSE: This study was conducted to evaluate the clinical peri-implant soft tissue changes during the first year after occlusal loading and the ridge base relation after 3 years for mandibular computer-aided design and computer-aided manufacturing (CAD-CAM) screw-retained implant-supported hybrid prosthesis of polyetheretherketone (PEEK) framework utilized with All-on-Four treatment concept. MATERIALS AND METHODS: Sixteen completely edentulous patients were rehabilitated by four implants following the All-on-Four protocol. After 3 months, the definitive prosthesis was constructed to be a screw-retained CAD-CAM milled framework from the modified PEEK (BioHPP), bonded to polymethylmethacrylate teeth and a pink shaded indirect light-polymerized nanofilled composite resin imitating the soft tissues. Peri-implant soft tissue changes regarding plaque, bleeding, gingival scores, and probing depth were evaluated at prosthesis insertion (T0), 6 months (T1), and 12 months (T2) after insertion. Also, monitoring of the ridge base relation was performed using cone beam computed tomography at time of insertion (T0), and 1 year (T1), 2 years (T2), and 3 years (T3) after mandibular fixed detachable All-on-Four framework insertion. Using Shapiro-Wilk tests using SPSS® software version 22 (SPSS Inc., Chicago, IL), all clinical data were nonparametric, while the ridge base relation data were parametric. RESULTS: There were statistically significant differences regarding a plaque, gingival, and bleeding scores for all implants with the advancement of time. However, there was a statistically insignificant difference regarding probing depth in the posterior implants (p = 0.581). Regarding ridge base relation, there was a significant difference between observation times only in the anterior ridge area in between the two anterior implants (p = 0.011). CONCLUSIONS: Within the limitations of the study, the full-arch PEEK framework of fixed-detachable, hybrid prosthesis used with the All-on-Four concept for rehabilitation of mandibular edentulous arches is an acceptable treatment approach. Based on the stable ridge base relation posteriorly found in this study, less stress is distributed to the underlining bone due to the shock-absorbing ability of PEEK. Special considerations for frequent soft tissue follow-up and regular maintenance of oral hygiene measures are recommended.

Effect of Ridge Splitting of Mandibular Knife Edge Ridges with Two-implant Retained Overdenture with Locator Attachments on Peri-implant Bone Level and Posterior Ridge Resorption: A One-year Preliminary Study.

AIM: This study was conducted to evaluate peri-implant bone height changes and posterior ridge resorption by using two-implant retained polyetheretherketone (PEEK) overdentures with locator attachments following expansion of mandibular knife edge ridges by ridge splitting. MATERIALS AND METHODS: Eighteen patients were selected for ridge splitting followed by expansion, implant placement, and bone graft application. Six months later, the fabrication of PEEK overdentures retained by locator attachments was accomplished. Friedman test, Wilcoxon signed-rank test, and Spearman correlation were used to evaluate the changes over time. RESULTS: Peri-implant bone height loss increased significantly with the advance of time between 6 and 12 months following denture insertion. Posterior area index changes were significant over time when measured at the time of denture insertion and twelve months following denture insertion. CONCLUSION: The effect of using PEEK as overdenture base material retained with two locator attachments allowed sharing the load between the peri-implant bone anteriorly and residual ridge posteriorly in cases with ridge splitting technique. CLINICAL SIGNIFICANCE: Using PEEK as an overdenture base material is a successful means of bone preservation. How to cite this article: Helmy MA, El-Shaheed NH, El Waseef FA, et al. Effect of Ridge Splitting of Mandibular Knife Edge Ridges with Two-implant Retained Overdenture with Locator Attachments on Peri-implant Bone Level and Posterior Ridge Resorption: A One-year Preliminary Study. J Contemp Dent Pract 2023;24(11):834-839.

COVID-19-associated neurological sequelae: A case series on cerebral microbleeds and encephalopathy.

BACKGROUND: Critical illness-associated cerebral microbleeds and leukoencephalopathy connected to coronavirus disease 2019 (COVID-19) infection are emerging areas of concern in current medical literature. METHODS: We reviewed cases of patients with COVID-19-associated neurological manifestations to study the prevalence and outcome of such conditions. Case Series Findings: Our review yielded seven distinct patients. Six exhibited cerebral microbleeds, primarily localized in the juxtacortical white matter and the corpus callosum. In contrast, one individual presented with leukoencephalopathy. Tragically, of these patients, five succumbed to their ailments. One was discharged with mild cognitive impairments, while another underwent a tracheostomy and was subsequently moved to a long-term care establishment. CONCLUSION: Our findings underscore the significance of neuro-radiological observations in those grappling with severe manifestations of COVID-19, drawing attention to the possible neurological repercussions of the virus.

Insights on gastrointestinal motility through the use of optogenetic sensors and actuators.

The muscularis of the gastrointestinal (GI) tract consists of smooth muscle cells (SMCs) and various populations of interstitial cells of Cajal (ICC), platelet-derived growth factor receptor α+ (PDGFRα+ ) cells, as well as excitatory and inhibitory enteric motor nerves. SMCs, ICC and PDGFRα+ cells form an electrically coupled syncytium, which together with inputs from the enteric nervous system (ENS) regulates GI motility. Early studies evaluating Ca2+ signalling behaviours in the GI tract relied upon indiscriminate loading of tissues with Ca2+ dyes. These methods lacked the means to study activity in specific cells of interest without encountering contamination from other cells within the preparation. Development of mice expressing optogenetic sensors (green calmodulin fusion protein (GCaMP), red calmodulin fusion protein (RCaMP)) has allowed visualization of Ca2+ signalling behaviours in a cell specific manner. Additionally, availability of mice expressing optogenetic modulators (channelrhodopsins or halorhodospins) has allowed manipulation of specific signalling pathways using light. GCaMP-expressing animals have been used to characterize Ca2+ signalling behaviours of distinct classes of ICC and SMCs throughout the GI musculature. These findings illustrate how Ca2+ signalling in ICC is fundamental in GI muscles, contributing to tone in sphincters, pacemaker activity in rhythmic muscles and relaying enteric signals to SMCs. Animals that express channelrhodopsin in specific neuronal populations have been used to map neural circuitry and to examine post junctional neural effects on GI motility. Thus, optogenetic approaches provide a novel means to examine the contribution of specific cell types to the regulation of motility patterns within complex multi-cellular systems.

Ca2+ signalling in interstitial cells of Cajal contributes to generation and maintenance of tone in mouse and monkey lower oesophageal sphincters.

The lower oesophageal sphincter (LES) generates tone and prevents reflux of gastric contents. LES smooth muscle cells (SMCs) are relatively depolarised, facilitating activation of Cav 1.2 channels to sustain contractile tone. We hypothesised that intramuscular interstitial cells of Cajal (ICC-IM), through activation of Ca2+ -activated Cl- channels (ANO1), set membrane potentials of SMCs favourable for activation of Cav 1.2 channels. In some gastrointestinal muscles, ANO1 channels in ICC-IM are activated by Ca2+ transients, but no studies have examined Ca2+ dynamics in ICC-IM within the LES. Immunohistochemistry and qPCR were used to determine expression of key proteins and genes in ICC-IM and SMCs. These studies revealed that Ano1 and its gene product, ANO1, are expressed in c-Kit+ cells (ICC-IM) in mouse and monkey LES clasp muscles. Ca2+ signalling was imaged in situ, using mice expressing GCaMP6f specifically in ICC (Kit-KI-GCaMP6f). ICC-IM exhibited spontaneous Ca2+ transients from multiple firing sites. Ca2+ transients were abolished by cyclopiazonic acid or caffeine but were unaffected by tetracaine or nifedipine. Maintenance of Ca2+ transients depended on Ca2+ influx and store reloading, as Ca2+ transient frequency was reduced in Ca2+ free solution or by Orai antagonist. Spontaneous tone of LES muscles from mouse and monkey was reduced ∼80% either by Ani9, an ANO1 antagonist or by the Cav 1.2 channel antagonist nifedipine. Membrane hyperpolarisation occurred in the presence of Ani9. These data suggest that intracellular Ca2+ activates ANO1 channels in ICC-IM in the LES. Coupling of ICC-IM to SMCs drives depolarisation, activation of Cav 1.2 channels, Ca2+ entry and contractile tone. KEY POINTS: The lower oesophageal sphincter (LES) generates contractile tone preventing reflux of gastric contents into the oesophagus. LES smooth muscle cells (SMCs) display depolarised membrane potentials facilitating activation of L-type Ca2+ channels. Interstitial cells of Cajal (ICC) express Ca2+ -activated Cl- channels encoded by Ano1 in mouse and monkey LES. Ca2+ signalling in ICC activates ANO1 currents in ICC. ICC displayed spontaneous Ca2+ transients in mice from multiple firing sites in each cell and no entrainment of Ca2+ firing between sites or between cells. Inhibition of ANO1 channels with a specific antagonist caused hyperpolarisation of mouse LES and inhibition of tone in monkey and mouse LES muscles. Our data suggest a novel mechanism for LES tone in which Ca2+ transient activation of ANO1 channels in ICC generates depolarising inward currents that conduct to SMCs to activate L-type Ca2+ currents, Ca2+ entry and contractile tone.

Intestinal microsporidiosis among HIV/AIDS patients receiving antiretroviral therapy in Sana'a city, Yemen: first report on prevalence and predictors.

BACKGROUND: Intestinal microsporidiosis is an opportunistic infection associated with persistent diarrhea among HIV/AIDS patients. In Yemen, however, its epidemiology is unknown. Therefore, this study determined its prevalence and predictors among HIV/AIDS patients receiving antiretroviral therapy (ART) in Sana'a city, the capital of Yemen. METHODS: This cross-sectional study included 402 patients receiving ART at Al-Jomhori Educational Hospital in Sana'a from November 2019 to December 2020. Data about demographics, clinical characteristics and risk factors were collected using a pre-designed questionnaire. Stool samples were collected and examined for microsporidian spores using the Gram-chromotrope Kinyoun staining. Blood samples were also collected and used for CD4 cell counting by flow cytometry. Univariate analysis was used to test the association of patients' characteristics and risk factors with intestinal microsporidiosis. Multivariable logistic regression was then used to identify the independent predictors of infection. Statistical significance was considered at P-values < 0.05. RESULTS: Intestinal microsporidiosis was prevalent among 14.2% (57/402) of HIV/AIDS patients and was significantly associated with diarrhea (OR 3.4, 95% CI 1.7-6.6; P = 0.001). The significant independent predictors of infection were < 200 CD4 cells/µl (AOR 3.2, 95% CI 1.5-6.9; P = 0.003), not washing hands after contacting soil (AOR 2.5, 95% CI 1.1-5.4; P = 0.026) and before eating (AOR 3.1, 95% CI 1.5-6.4; P = 0.003), eating unwashed raw produce (AOR 2.5, 95% CI 1.2-5.3; P = 0.017) and absence of indoor latrines (AOR 6.2, 95% CI 1.5-25.9; P = 0.012). CONCLUSIONS: The prevalence of intestinal microsporidiosis among HIV/AIDS patients in Sana'a is high and comparable to that reported from several other countries, being prevalent among approximately 14.0% of patients and significantly associated with diarrhea. It could be predicted among patients who have < 200 CD4 cells/µl, have poor hand hygiene after contacting soil and before eating, usually eat unwashed raw produce, or do not possess indoor latrines. Large-scale studies on its epidemiology and predictors among HIV/AIDS patients across the country are warranted.

Ca2+ Signaling Is the Basis for Pacemaker Activity and Neurotransduction in Interstitial Cells of the GI Tract.

Years ago gastrointestinal motility was thought to be due to interactions between enteric nerves and smooth muscle cells (SMCs) in the tunica muscularis. Thus, regulatory mechanisms controlling motility were either myogenic or neurogenic. Now we know that populations of interstitial cells, c-Kit+ (interstitial cells of Cajal or ICC), and PDGFRα+ cells (formerly "fibroblast-like" cells) are electrically coupled to SMCs, forming the SIP syncytium. Pacemaker and neurotransduction functions are provided by interstitial cells through Ca2+ release from the endoplasmic reticulum (ER) and activation of Ca2+-activated ion channels in the plasma membrane (PM). ICC express Ca2+-activated Cl- channels encoded by Ano1. When activated, Ano1 channels produce inward current and, therefore, depolarizing or excitatory effects in the SIP syncytium. PDGFRα+ cells express Ca2+-activated K+ channels encoded by Kcnn3. These channels generate outward current when activated and hyperpolarizing or membrane-stabilizing effects in the SIP syncytium. Inputs from enteric and sympathetic neurons regulate Ca2+ transients in ICC and PDGFRα+ cells, and currents activated in these cells conduct to SMCs and regulate contractile behaviors. ICC also serve as pacemakers, generating slow waves that are the electrophysiological basis for gastric peristalsis and intestinal segmentation. Pacemaker types of ICC express voltage-dependent Ca2+ conductances that organize Ca2+ transients, and therefore Ano1 channel openings, into clusters that define the amplitude and duration of slow waves. Ca2+ handling mechanisms are at the heart of interstitial cell function, yet little is known about what happens to Ca2+ dynamics in these cells in GI motility disorders.

New pyrimidine/thiazole hybrids endowed with analgesic, anti-inflammatory, and lower cardiotoxic activities: Design, synthesis, and COX-2/sEH dual inhibition.

Some cyclooxygenase (COX)-2 selective medications were withdrawn from the market just a few years after their production due to cardiovascular side effects. In this study, a new series of pyrimidine/thiazole hybrids 7a-p was synthesized as selective COX-2/soluble epoxide hydrolase (sEH) inhibitors with analgesic and anti-inflammatory effects, and lower cardiotoxicity effects. The target compounds were synthesized and in vitro tested against COX-1, COX-2, and sEH enzymes. Hybrids 7j, 7k, and 7i showed the greatest COX-2-inhibitory activity and were discovered to be the most potent dual COX-2/sEH inhibitors. In vivo tests revealed that these hybrids were the most active analgesic/anti-inflammatory agents, with improved ulcerogenic and cardioprotective properties. Finally, the most active dual inhibitors were docked into COX-2/sEH active regions to explain their binding mechanisms.

Polyetheretherketone subperiosteal implant retaining a maxillary fixed prosthesis: A case series.

STATEMENT OF PROBLEM: Patients needing dental rehabilitation of a complete atrophic maxilla would benefit from simplified treatment plans. PURPOSE: The purpose of this case series was to demonstrate the prosthetic management of 4 edentulous patients with severe maxillary ridge resorption who declined multiple stage surgery and sought a fixed prosthesis in single-stage surgery. MATERIAL AND METHODS: The patients were provided with completely digital computer-aided designed and computer-aided manufactured (CAD-CAM) polyetheretherketone (PEEK) maxillary subperiosteal frameworks, which were surgically placed in a 1-step procedure. The patients were followed up for 12 months and evaluated for signs of implant rejection, infection, prosthetic fracture or mobility, or implant exposure. RESULTS: At the 12-month follow-up, all the implants were functionally stable with healthy soft tissue and showed no sign of prosthetic fracture, infection, or pus discharge. CONCLUSIONS: PEEK subperiosteal implants for maxillary atrophied ridges can be considered a promising treatment option within the limitations of this clinical study with low patient numbers and a short observational time.

Multivariate statistics explaining groundwater chemistry, Asyut, Egypt.

Groundwater is an important source for domestic and irrigation purposes in Asyut area. Water quality varied widely due to complex geochemical processes and pollution sources. Understanding the processes controlling groundwater chemistry is necessary to overcome related problems. Multivariate statistics revealed that groundwater is affected by anthropogenic recharge (agricultural/organic pollution), mineralization, and redox processes. Contributions from natural vs. anthropogenic sources explain the variance in hydrochemical data. Shallow wells are relatively higher in bicarbonate content due to oxidation of organic pollutants. Shallow wells anomaly high with iron and organically polluted are most probably owing to pipe corrosion in residential areas. N fertilization impact on natural weathering has been demonstrated. Groundwater is getting more mineralized toward desert fringes due to lithological and hydrogeological characteristics under unconfined conditions. Evaporation factor enhances groundwater salinity under aridity. Fe and Mn contents are relatively higher as the redox potential is getting more reducing. The current study will help in building suitable management plan to protect the aquifer.