Placement of immediate dental implants in extraction sockets exhibiting the apical pathosis. A meta-analysis.

Objectives: It is commonly accepted that immediate implantation is the best option for patients since it shortens the time patients must wait for ultimate restoration and provides a predictable functional and aesthetic result. However, this approach is still controversial in patients with apical pathosis. The goal of this systematic review and meta-analysis was to determine the efficacy of immediate implant insertion in patients with apical pathosis. Material and methods: Between 2000 and 2023, PRISMA-compliant keywords were used to search PubMed, MEDLINE, CENTRAL, and the Cochrane Library. All English-language clinical studies that met PICOS criteria were included in a manual search. The included studies' demographic profile and event data for immediate dental implantation success in patients with or without apical pathosis were meta-analyzed using RevMan. The implant survival rate was assessed using risk ratio of plaque index and bleeding index. Begg's test using MedCalc and RevMan risk of bias assessment assessed publication bias. Results: A meta-analysis of 10 trials with 849 dental implantation patients found a substantial difference in initial implant placement success rates in infected sites. The pooled risk ratio for plaque index is 0.59 (95% CI: 0.36-0.96) with heterogeneity of Tau2 = 0.62, chi2 = 109.69, df = 11, I2 = 90%, z = 2.12, and p < 0.05. While, the pooled risk ratio for bleeding index is 0.77 (95% CI: 0.60 to 0.98) with Tau2 = 0.16, chi2 = 103.67, df = 11, I2 = 89%, z = 2.12, and p < 0.05. The pooled odds ratio of implant survival rate is 2.08 (95% CI: 1.56 to 1.79) with Tau2 0.16; chi2 52.43; df 9; I2 83%; z 4.93 and p < 0.05. As evidenced by the funnel plot and statistically insignificant Begg's test p values of 0.45. Conclusion: The placement of immediate implants in locations affected by apical pathosis is a clinically beneficial surgery, resulting in favorable aesthetic and functional outcomes for patients.

Cost Consequence Analysis of Belimumab versus Standard of Care for the Management of Systemic Lupus Erythematosus in Saudi Arabia: A Retrospective Cohort Study.

BACKGROUND: Belimumab use for the management of systemic lupus erythematosus (SLE) has been limited, in part due to its high acquisition cost relative to the standard of care (SoC) and the uncertainties about its cost-effectiveness. Therefore, the aim of this study was to compare the cost and effectiveness of belimumab versus the SoC alone for the management of SLE using real-world data from the perspective of public healthcare payers in Saudi Arabia. METHODS: Data were retrieved from a national prospective cohort of SLE, Saudi Arabia. Adult SLE patients (≥18 yrs.) treated with belimumab plus the SoC or the SoC alone for at least six months were recruited. The effectiveness was measured using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Unit costs for health services and prescription drugs were retrieved from the Saudi ministry of health. Nonparametric bootstrapping with inverse probability weighting was conducted to generate the 95% confidence limits for the cost and effectiveness. RESULTS: A total of 15 patients on belimumab plus the SoC and 41 patients on the SoC alone met the inclusion criteria and were included in the analysis. The majority of patients were females (91.07%) with a mean age of 38 years. The mean difference in cost and SLEDAI-2K score reduction between belimumab versus the SoC were USD 5303.16 [95% CI: USD 2735.61-USD 7802.52] and 3.378 [95% CI: 1.769-6.831], respectively. Belimumab demonstrated better effectiveness but higher cost in 96% of the bootstrap cost-effectiveness distributions. CONCLUSION: Future studies should use more robust research designs and a larger sample size to confirm the findings of this study.

The Diagnostic Yield of Abdominal Ultrasounds Requested by Family Physicians at an Academic Hospital in Riyadh, Saudi Arabia.

BACKGROUND: Abdominal ultrasound is a non-invasive, relatively inexpensive, and widely available diagnostic modality in family medicine settings. OBJECTIVES: Our study aimed to identify the most common indications for requesting abdominal ultrasounds by family physicians, determine the frequency of abdominal ultrasound with abnormal findings, identify the most common findings, and determine patients' characteristics associated with abnormal findings. METHODS: This retrospective chart-based study was conducted from January 2020 to June 2020 to analyze patients' abdominal ultrasounds reports requested by family physicians in 2019 at King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. RESULTS: We assessed abdominal ultrasound reports of 1,113 patients. There were 620 (55.7%) female patients. The mean age and body mass index (BMI) were 46.35 years ± 15.04 and 29.33 kg/m2 ± 7.06, respectively. The most common indications were abdominal pain (43.2%), suspicion of gallbladder and biliary system diseases (18.5%), and abnormal liver function tests (14.6%). The frequency of abnormal findings was 793 (71.2%), and the most common findings were fatty liver infiltration (49.7%), liver enlargement (20.1%), and gallstones (13.3%). Females had a lower likelihood to have abnormal findings compared to males (odds ratio (OR)=0.688, p=0.009). Lastly, the likelihood of abnormal findings increased with age and was highest among patients aged 71 years or more (OR=25.9, p< 0.001). CONCLUSION: Abnormal findings were more prevalent in our study compared with other studies. Abnormal findings were more common among males and older age groups. We recommend future studies on patients from community-based family medicine settings, and to examine the association of abnormal findings with patient-centered endpoints. Finally, disseminating the results of this study will inform family physicians with the most common abnormal abdominal ultrasound findings, and will enhance the discussion with patients undergoing an abdominal ultrasound examination.

Darunavir: A comprehensive profile.

Darunavir: (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl [(2S,3R)-4-{[(4-aminophenyl)sulfonyl] (isobutyl)amino}-3-hydroxy-1-phenyl-2-butanyl]carbamate is a synthetic non-peptide protease inhibitor. On June 2006, it was first approved by the Food and Drug administration (FDA) for treatment of resistant type-1 of the human immunodeficiency virus (HIV). In July 2016, the FDA expanded the approval for use of darunavir in pregnant women with HIV infection. Darunavir prevents the replication of HIV virus by inhibiting the catalytic activity of the HIV-1 protease enzyme, and selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus-infected cells, which prevents the formation of mature infectious virus particles. Darunavir is unique among currently available protease inhibitors because it maintains antiretroviral activity against a variety of multidrug-resistant HIV strains. This article discusses, by a critical extensive review of the literature, the description of darunavir in terms of its names, formulae, elemental composition, appearance, and use in the treatment of HIV-infected patients. The article also discusses the methods for preparation of darunavir, its physical-chemical properties, analytical methods for its determination, pharmacological properties, and dosing information.

Growth hormone transgenesis in coho salmon disrupts muscle immune function impacting cross-talk with growth systems.

Suppression of growth during infection may aid resource allocation towards effective immune function. Past work supporting this hypothesis in salmonid fish revealed an immune-responsive regulation of the insulin-like growth factor (IGF) system - an endocrine pathway downstream of growth hormone (GH). Skeletal muscle is the main target for growth and energetic storage in fish, yet little is known about how its growth is regulated during an immune response. We addressed this knowledge gap by characterising muscle immune responses in size-matched coho salmon (Oncorhynchus kisutch) achieving different growth rates. We compared a wild-type strain with two GH transgenic groups from the same genetic background achieving either maximal or suppressed growth - a design separating GH's direct effects from its influence on growth rate and nutritional state. Fish were sampled 30 h post-injection with phosphate-buffered saline (control) or mimics of bacterial or viral infection. We quantified mRNA expression levels for genes from the GH, GH receptor, IGF hormone, IGF1 receptor and IGF-binding protein families, along with immune genes involved in inflammatory or antiviral responses and muscle growth status marker genes. We demonstrate dampened immune function in GH transgenics compared with wild-type. The muscle of GH transgenics achieving rapid growth showed no detectable antiviral response, coupled with evidence of a constitutive inflammatory state. GH and IGF system gene expression was strongly altered by GH transgenesis and fast growth, both for baseline expression and responses to immune stimulation. Thus, GH transgenesis strongly disrupts muscle immune status and normal GH and IGF system expression responses to immune stimulation.

The complete salmonid IGF-IR gene repertoire and its transcriptional response to disease.

The insulin-like growth factor (IGF) receptor (IGF-IR) is necessary for IGF signalling and has essential roles in cellular growth. In teleost fish, two distinct IGF-IR duplicates are conserved called IGF-IRa and IGF-IRb. However, while a salmonid-specific whole genome duplication (ssWGD) is known to have expanded several key genes within the IGF axis, its impact on the IGF-IR repertoire remains unresolved. Using bioinformatic and phylogenetic approaches, we establish that salmonids retain two IGF-IRa paralogues from ssWGD and a single IGF-IRb copy. We measured the tissue-specific and developmental transcriptional regulation of each IGF-IR gene, revealing tight co-expression between the IGF-IRa paralogues, but expression divergence comparing IGF-IRa and IGF-IRb genes. We also examined the regulation of each IGF-IR gene in fish challenged by bacterial and viral infections, adding to recent reports that the IGF axis has roles linking growth and immunity. While whole salmonid fry showed a small upregulation of IGF-IR expression during both types of infection, bacterial challenge caused striking downregulation of IGF-IRa1 and IGF-IRa2 in head kidney and spleen of adult fish, alongside genes coding IGF hormones, highlighting a strong repression of IGF-signalling in primary immune tissues. The reported immune-responsive regulation of IGF-IR genes adds to an emerging body of evidence that supports important cross-talk between master growth and immune pathways in vertebrates.

Cross Talk Between Growth and Immunity: Coupling of the IGF Axis to Conserved Cytokine Pathways in Rainbow Trout.

Although disease and infection is associated with attenuated growth, the molecular pathways involved are poorly characterized. We postulated that the IGF axis, a central governor of vertebrate growth, is repressed during infection to promote resource reallocation towards immunity. This hypothesis was tested in rainbow trout (Oncorhynchus mykiss) challenged by Aeromonas salmonicida (AS), a Gram-negative bacterial pathogen, or viral hemorrhagic septicemia virus (VHSv) at hatch, first feeding, and 3 weeks after first feeding. Quantitative transcriptional profiling was performed for genes encoding both IGF hormones, 19 salmonid IGF binding proteins (IGFBPs) and a panel of marker genes for growth and immune status. There were major differences in the developmental response of the IGF axis to AS and VHSv, with the VHSv challenge causing strong down-regulation of many genes. Despite this, IGFBP-1A1 and IGFBP-6A2 subtypes, each negative regulators of IGF signaling, were highly induced by AS and VHSv in striking correlation with host defense genes regulated by cytokine pathways. Follow-up experiments demonstrated a highly significant coregulation of IGFBP-1A1 and IGFBP-6A2 with proinflammatory cytokine genes in primary immune tissues (spleen and head kidney) when trout were challenged by a different Gram-negative bacterium, Yersinia ruckeri. Based on our findings, we propose a model where certain IGFBP subtypes are directly regulated by cytokine signaling pathways, allowing immediate modulation of growth and/or immune system phenotypes according to the level of activation of immunity. Our findings provide new and comprehensive insights into cross talk between conserved pathways regulating teleost growth, development, and immunity.

Disparate developmental patterns of immune responses to bacterial and viral infections in fish.

During early stages of development vertebrates rely on an immature immune system to fight pathogens, but in non mammalian species few studies have taken an in-depth analysis of the transition from reliance on innate immune mechanisms to the appearance of adaptive immunity. Using rainbow trout as a model we characterized responses to two natural pathogens of this species, the Gram negative bacterium Aeromonas salmonicida and the virus VHSV, using microarray analysis at four early life history stages; eyed egg, post hatch, first feeding and three weeks post first feeding when adaptive immunity starts to be effective. All stages responded to both infections, but the complexity of the response increased with developmental stage. The response to virus showed a clear interferon response only from first feeding. In contrast, bacterial infection induced a marked response from early stages, with modulation of inflammatory, antimicrobial peptide and complement genes across all developmental stages. Whilst the viral and bacterial responses were distinct, there were modulated genes in common, mainly of general inflammatory molecules. This work provides a first platform to explore the development of fish immunity to infection, and to compare the age-dependent changes (from embryo to adults) across vertebrates.

Cold-induced changes in stress hormone and steroidogenic transcript levels in cunner (Tautogolabrus adspersus), a fish capable of metabolic depression.

The cunner (Tautogolabrus adspersus) is a fish with a wide latitudinal distribution that is capable of going into metabolic depression during the winter months, and thus, represents a unique model to investigate the impacts of cold temperatures on the stress response. In this study, we measured resting (pre-stress) plasma cortisol levels in 10 °C and 0 °C acclimated cunner from Newfoundland, and both catecholamine and cortisol levels after they were given a standardized handling stress (i.e. 1 min air exposure). In addition, we cloned and characterized cDNAs for several key genes of the cortisol-axis [cytochrome P450scc, steroidogenic acute regulatory protein (StAR) and a glucocorticoid receptor (GR) most likely to be an ortholog of the teleost GR2], determined the tissue distribution of their transcripts, and measured their constitutive (i.e. pre-stress) transcript levels in individuals acclimated to both temperatures. In cunner acclimated to 0 °C, post-stress epinephrine and norepinephrine levels were much lower (by approximately 9- and 5-fold, respectively) compared to 10 °C acclimated fish, and these fish had relatively low resting cortisol levels (~15 ngml(-1)) and showed a typical post-stress response. In contrast, those acclimated to 10 °C had quite high resting cortisol levels (~75 ngml(-1)) that actually decreased (to ~20 ngml(-1)) post-stress before returning to pre-stress levels. Finally, fish acclimated to 10 °C had higher P450scc transcript levels in the head kidney and lower levels of GR transcript in both the head kidney and liver. Taken together, these results suggest that: (1) temperature has a profound effect on the stress response of this species; and (2) although the ancestors of this species inhabited warm waters (i.e. they are members of the family Labridae), populations of cunner from colder regions may show signs of stress at temperatures as low as 10 °C.

Metabolic depression in cunner (Tautogolabrus adspersus) is influenced by ontogeny, and enhances thermal tolerance.

To examine the effect of ontogeny on metabolic depression in the cunner (Tautogolabrus adspersus), and to understand how ontogeny and the ability to metabolically depress influence this species' upper thermal tolerance: 1) the metabolic rate of 9°C-acclimated cunner of three size classes [0.2-0.5 g, young of the year (YOY); 3-6 g, small; and 80-120 g, large (adult)] was measured during a 2°C per day decrease in temperature; and 2) the metabolic response of the same three size classes of cunner to an acute thermal challenge [2°C h(-1) from 10°C until Critical Thermal Maximum, CTMax] was examined, and compared to that of the Atlantic cod (Gadus morhua). The onset-temperature for metabolic depression in cunner increased with body size, i.e. from 5°C in YOY cunner to 7°C in adults. In contrast, the extent of metabolic depression was ∼80% (Q10 = ∼15) for YOY fish, ∼65% (Q10 = ∼8) for small fish and ∼55% (Q10 = ∼5) for adults, and this resulted in the metabolic scaling exponent (b) gradually increasing from 0.84 to 0.92 between 9°C to 1°C. All size classes of cunner had significantly (approximately 60%) lower routine metabolic rates at 10°C than Atlantic cod. However, there was no species' difference in the temperature-induced maximum metabolic rate, and this resulted in factorial metabolic scope values that were more than two-fold greater for cunner, and CTMax values that were 6-9°C higher (∼21 vs. 28°C). These results: 1) show that ontogeny influences the temperature of initiation and the extent of metabolic depression in cunner, but not O2 consumption when in a hypometabolic state; and 2) suggest that the evolution of cold-induced metabolic depression in this northern wrasse species has not resulted in a trade-off with upper thermal tolerance, but instead, an enhancement of this species' metabolic plasticity.