Photobiomodulation and mesenchymal stem cell-conditioned medium for the repair of experimental critical-size defects.

Orthopedic surgeons face a significant challenge in treating critical-size femoral defects (CSFD) caused by osteoporosis (OP), trauma, infection, or bone tumor resections. In this study for the first time, the application of photobiomodulation (PBM) and bone marrow mesenchymal stem cell-conditioned medium (BM-MSC-CM) to improve the osteogenic characteristics of mineralized bone scaffold (MBS) in ovariectomy-induced osteoporotic (OVX) rats with a CSFD was tested. Five groups of OVX rats with CSFD were created: (1) Control (C); (2) MBS; (3) MBS + CM; (4) MBS + PBM; (5) MBS + CM + PBM. Computed tomography scans (CT scans), compression indentation tests, and histological and stereological analyses were carried out after euthanasia at 12 weeks following implantation surgery. The CT scan results showed that CSFD in the MBS + CM, MBS + PBM, and MBS + CM + PBM groups was significantly smaller compared to the control group (p = 0.01, p = 0.04, and p = 0.000, respectively). Moreover, the CSFD size was substantially smaller in the MBS + CM + PBM treatment group than in the MBS, MBS + CM, and MBS + PBM treatment groups (p = 0.004, p = 0.04, and p = 0.01, respectively). The MBS + PBM and MBS + CM + PBM treatments had significantly increased maximum force relative to the control group (p = 0.01 and p = 0.03, respectively). Bending stiffness significantly increased in MBS (p = 0.006), MBS + CM, MBS + PBM, and MBS + CM + PBM treatments (all p = 0.004) relative to the control group. All treatment groups had considerably higher new trabecular bone volume (NTBV) than the control group (all, p = 0.004). Combined therapies with MBS + PBM and MBS + CM + PBM substantially increased the NTBV relative to the MBS group (all, p = 0.004). The MBS + CM + PBM treatment had a markedly higher NTBV than the MBS + PBM (p = 0.006) and MBS + CM (p = 0.004) treatments. MBS + CM + PBM, MBS + PBM, and MBS + CM treatments significantly accelerated bone regeneration of CSFD in OVX rats. PBM + CM enhanced the osteogenesis of the MBS compared to other treatment groups.

Sexual function among women with vaginismus: a biopsychosocial approach.

BACKGROUND: Vaginismus is known as a type of sexual pain disorder. Regarding the multifactorial nature of vaginismus, the biopsychosocial model is one of the best models to describe this sexual disorder. AIM: The present research was conducted to study the determinants of sexual function in women with and without vaginismus based on the biopsychosocial model. METHODS: This case-control study was conducted in Iran on 420 women with and without primary vaginismus who met the inclusion criteria. All eligible people were included in the research once their eligibility was verified and their informed permission was acquired; convenience and purposive sampling techniques were used continually. Data collection tools included the demographic and obstetric information form and multiple published scales and questionnaires. Structural equation modeling with LISREL 9.2 software (Scientific Software International) was used to evaluate the determinants of the sexual function of vaginismus. OUTCOMES: Participants rated their determinants of sexual function based on the biopsychosocial model. RESULTS: The mean ages of the case and control groups were 27.67 and 28.44 years, respectively. The direct, indirect, and total effects of the dimensions of sexual health on sexual function and the diagnostic score of vaginismus of the women with vaginismus were significant (P < .001). Furthermore, based on the results, the diagnostic score of vaginismus in women with vaginismus was significantly affected by the direct, indirect, and cumulative impacts of vaginal penetration cognition and fear of sex (P = .016, P = .005). Women with and without vaginismus were able to accept the models' excellent fit. CLINICAL IMPLICATIONS: This study helps inform health planners and policy makers about the sexual function of women with vaginismus, the factors related to this disorder, and the multidimensional nature of this sexual problem. STRENGTHS AND LIMITATIONS: This study attempted to offer a more comprehensive and complete view of present knowledge via surveying different aspects of sexual health and by means of valid and reliable tools and path analysis. The study's merits include the use of the biopsychosocial model to evaluate sexual function in women with vaginismus, the use of a variety of questionnaires to compare women with and without vaginismus, and the size of the sample. The research was limited by the fact that electronic sampling was conducted because of the COVID-19 epidemic. CONCLUSION: Based on the findings of the present study for the group of women with vaginismus, the direct, indirect, and overall effects of the majority of dimensions of sexual health were significantly correlated with sexual function and vaginismus.

Consecutive Alkylation, "Click", and "Clip" Reactions for the Traceless Methionine-Based Conjugation and Release of Methionine-Containing Peptides.

"Click" reactions have revolutionized research in many areas of science. However, a disadvantage of the high stability of the Click product is that identifying simple treatments for cleanly dissociating the latter under the same guiding principles, i.e., a "Clip" reaction, remains a challenge. This study demonstrates that electron-deficient alkynes, conveniently installed on methionine residues, can participate in well-known Click (nucleophilic thiol-allene addition) and subsequent Clip reactions (radical thiol-ene addition). To illustrate this concept, a variety of bioconjugates (peptide-peptide; peptide-fluorophore; peptide-polymer; and peptide-protein) were prepared. Interestingly, the Clip reaction of these bioconjugates releases the original peptides concurrent with regeneration of their unmodified methionine residue, in minutes. Moreover, the conjugates demonstrate substantial stability toward endogenous levels of reactive species in bacteria, illustrating the potential for this chemistry in the biosciences. The reaction conditions employed in the Click and Clip steps are compatible with the preservation of the integrity of biomolecules/fluorophores and involve readily accessible reagents and the natural functional groups on peptides/proteins.

ANXA2, SP17, SERPINA5, PRDX2 genes, and sperm DNA fragmentation differentially represented in male partners of infertile couples with normal and abnormal sperm parameters.

This study aims to evaluate the expression of genes associated with the fertilisation potential and embryo development, sperm DNA fragmentation (SDF), and acrosome reaction in male partners of infertile couples with different sperm parameters compared to fertile men. First, male partners of infertile couples with abnormal (N = 25) and normal sperm parameters (N = 25), and fertile men (N = 10) were included in experimental groups I, II, and controls respectively. The mRNA levels of the Annexin A2 (ANXA2), Sperm protein 17 (SP17), Plasma serine protease inhibitor (SERPINA5), and Peroxiredoxin-2 (PRDX2) genes and SDF were evaluated. To evaluate the maturity of the sperm and oxidative stress, the acrosome reaction, the lipid peroxidation, and total antioxidant were measured. As result, SP17 showed a significantly lower expression in both experimental groups. SERPINA5 was significantly down-regulated in experimental group I that was aligned with the low rate of acrosome reaction. Significant overexpression of PRDX2 was found between experimental group II and controls. Significant higher rates of SDF were seen in both experimental groups compared to the controls. Finally, our data suggest that differentially gene expression of SP17 is a potential diagnostic biomarker in infertile men either with normal or abnormal sperm parameters. SDF is one of the causes of male infertility, independent of the sperm parameters.

Improved healing of critical-size femoral defect in osteoporosis rat models using 3D elastin/polycaprolactone/nHA scaffold in combination with mesenchymal stem cells.

Osteoporosis is a common bone disease that results in elevated risk of fracture, and delayed bone healing and impaired bone regeneration are implicated by this disease. In this study, Elastin/Polycaprolactone/nHA nanofibrous scaffold in combination with mesenchymal stem cells were used to regenerate bone defects. Cytotoxicity, cytocompatibility and cellular morphology were evaluated in vitro and observations revealed that an appropriate environment for cellular attachment, growth, migration, and proliferation is provided by this scaffold. At 3 months following ovariectomy (OVX), the rats were used as animal models with an induced critical size defect in the femur to evaluate the therapeutic potential of osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) seeded on 3 dimension (3D) scaffolds. In this experimental study, 24 female Wistar rats were equally divided into three groups: Control, scaffold (non-seeded BM-MSC), and scaffold + cell (seeded BM-MSC) groups. 30 days after surgery, the right femur was removed, and underwent a stereological analysis and RNA extraction in order to examine the expression of Bmp-2 and Vegf genes. The results showed a significant increase in stereological parameters and expression of Bmp-2 and Vegf in scaffold and scaffold + cell groups compared to the control rats. The present study suggests that the use of the 3D Elastin/Polycaprolactone (PCL)/Nano hydroxyapatite (nHA) scaffold in combination with MSCs may improve the fracture regeneration and accelerates bone healing at the osteotomy site in rats.

Resveratrol suppresses interleukin-6 expression through activation of sirtuin 1 in hypertrophied H9c2 cardiomyoblasts.

Inflammatory cytokine, interleukin-6 (IL-6), plays an important role in the pathogenesis of cardiac hypertrophy. Recent studies have documented that resveratrol exhibits cardioprotective effects. The present study attempts to explore whether resveratrol suppreses IL-6 in hypertrophied H9c2 cardiomyoblasts through histone deacetylase, sirtuin 1 (SIRT1). To induce hypertrophy, the cells were incubated with angiotensin II (Ang II). Treatment groups were treated with different doses (1, 10, 25, 50, 75, and 100 µM) of resveratrol (R). Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell size was determined using crystal violet staining. Gene expression was assessed by real-time polymerase chain reaction technique. Enzyme-linked immunosorbent assay was used to measure IL-6 concentration. The results showed that cell area and ANP messenger RNA (mRNA) levels decreased significantly in R25+Ang, R50+Ang, and R100+Ang groups, as compared with Ang group. Therefore, 10, 20, 30, 40, and 50 µM of resveratrol were used to to evaluate its anti-inflammatory effects. The results revealed that Ang II upregulated IL-6 at both mRNA and protein levels (p < .001 vs. normal) and resveratrol (50 µM) decreased IL-6 mRNA (p < .01) and protein (p < .05) significantly in comparison to Ang group. However, in groups in which the cells were pretreated with SIRT1 inhibitor, EX-527, the response of resveratrol was partially reversed. Transcription levels of IL-6 receptor components (gp130 and gp80) did not change significantly among the experimental groups. The current data suggests that resveratrol protects H9c2 cells against Ang II-induced hypertrophy by suppression of IL-6 through SIRT1 activation.

Preconditioning adipose-derived stem cells with photobiomodulation significantly increased bone healing in a critical size femoral defect in rats.

We assessed the combined impacts of human demineralized bone matrix (hDBM) scaffold, adipose-derived stem cells (hADS), and photobiomodulation (PBM) on bone repair of a critical size femoral defect (CSFD) in 72 rats. The rats were divided into six groups: control (group 1); ADS (group 2 - ADS transplanted into hDBM); PBM (group 3 - PBM-treated CSFDs); ADS + PBM in vivo (group 4 - ADS transplanted into hDBM and the CSFDs were treated with PBM in vivo); ADS + PBM in vitro (group 5 - ADS were treated with PBM in vitro, then seeded into hDBM); and ADS + PBM in vitro+in vivo (group 6 - PBM-treated ADS were seeded into hDBM, and the CSFDs were treated with PBM in vivo. At the anabolic phase (2 weeks after surgery), bone strength parameters of the groups 5, 6, and 4 were statistically greater than the control, ADS, and PBM in vivo groups (all, p = 0.000). Computed tomography (CT) scans during the catabolic phase (6 weeks after surgery) of bone healing revealed that the Hounsfield unit (HU) of CSFD in the groups 2 (p = 0.000) and 5 (p = 0.019) groups were statistically greater than the control group. The groups 5, 4, and 6 had significantly increased bone strength parameters compared with the PBM in vivo, control, and ADS groups (all, p = 0.000). The group 5 was statistically better than the groups 4, and 6 (both, p = 0.000). In vitro preconditioned of hADS with PBM significantly increased bone repair in a rat model of CSFD in vivo.

Combined therapy of adipose-derived stem cells and photobiomodulation on accelerated bone healing of a critical size defect in an osteoporotic rat model.

We investigated the impact of human demineralized bone matrix (hDBM) plus adipose-derived stem cells (hADS) plus photobiomodulation (PBM) on a critical-sized femoral defect (CSFD) in ovariectomy induced osteoporosis in rats. There were 6 groups as follows. In group 1 (control, C), only CSFDs were created. Groups 2-6 were implanted with DBM into the CSFD (DBM-CSFD). In group 2 (S), only DBM was transplanted into the CSFD. In group 3 (S + PBM), the DBM-CSFDs were treated with PBM. In group 4, the DBM-CSFDs were treated with alendronate (S + ALN). In group 5, ADSs were seeded into DBM-CSFD (S + ADS). In group 6, ADSs were seeded into DBM-CSFD and the CSFDs were treated with PBM (S + PBM + ADS). At week eight (catabolic phase of bone repair), the S + ALN, S + PBM + ADS, S + PBM, and S + ADS groups all had significantly increased bone strength than the S group (ANOVA, p = 0.000). The S + PBM, S + PBM + ADS, and S + ADS groups had significantly increased Hounsfield unit than the S group (ANOVA, p = 0.000). ALN, ADS, and PBM significantly increased healed bone strength in an experimental model of DBM-treated CSFD in the catabolic phase of bone healing in osteoporotic rats. However, ALN alone and PBM plus ADS were superior to the other protocols.

The impact of irritable bowel syndrome on health-related quality of life in women with polycystic ovary syndrome.

BACKGROUND: The objectives of this study were to compare the prevalence and quality of life (QOL) of irritable bowel syndrome (IBS) in women with polycystic ovary syndrome (PCOS) compared with healthy women. METHODS: This was a case-control study of 201 women recruited at an infertility clinic in Iran. The control group were healthy women (n = 100) and the comparison group, women with PCOS (n = 101). Data were collected by clinical Rome III criteria to determine the IBS, Bristol scale for stool consistency and IBS QOL. RESULTS: The reporting of IBS symptoms were higher in PCOS (20.7%) than control group (11%) (P = 0.05). The IBS QOL score in the IBS + PCOS group was lower than other groups (IBS+ non PCOS, non IBS + PCOS, non IBS+ non PCOS; scores in food avoidance and worries about health domains were significant (P < 0.01). CONCLUSIONS: We conclude that having PCOS and an increased level of LH/FSH tends to cause IBS symptoms. IBS + PCOS women experience significant impaired quality of life scores particularly in relation to worries about health and food avoidance. These results offer further insights into IBS in PCOS women and their functional status and wellbeing.

Paroxetine modulates immune responses by activating a JAK2/STAT3 signaling pathway.

Paroxetine, a representative of serotonin reuptake inhibitors, has recently gained attention due to its anti-inflammatory properties. However, underlying mechanisms responsible for its immunosuppressive effects remain to be unveiled. To understand the responsible signaling mechanisms, we examined paroxetine's effect on the Janus kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) signaling pathway on lipopolysaccharide + phytohemagglutinin-induced human peripheral blood mononuclear cells culture. We also evaluate the possible dependency of paroxetine immunomodulation effects on the 5-HT system of immune cells. Our results indicated that paroxetine attenuates proinflammatory cytokine production (interleukin-1ß [IL-1ß], IL-17, and tumor necrosis factor-α) and increases expression of IL-10 and JAK2/STAT3 evidence for macrophages polarization to M2 subset and functional dendritic cells depletion. In conclusion, paroxetine can exert its anti-inflammatory effects via both the 5-HT systems present in immune cells and the JAK2-STAT3 pathway. Our results also suggest that paroxetine exerted its immunosuppressive effects partially via serotonin. Nonetheless, JAK2/STAT3-modulated paroxetine effects were independent of serotonin, hence sufficiently applicable for inflammation repression.

Identifying dimensions of empowerment in patients with inflammatory bowel disease: a qualitative study.

The role of patients' empowerment in enhancing the quality of life of chronic patients is undeniable and its importance in health policy making and health care is increasing day by day. However, no guidelines have been defined to empower people with inflammatory bowel disease (IBD). The purpose of this study was to identify the dimensions of IBD patients' empowerment. Semi-structured interviews were conducted with 26 participants who were purposefully selected from 2 IBD clinics in Tehran and Shiraz cities to gain diversity in the clinical and demographic characteristics. The data were analyzed based on the Granheim and Landman's content analysis method. According to the result of this study, the empowerment of IBD patients is composed of five dimensions including self-care, psychological coping with disease, social interaction skills, disease-specific health literacy and self-evaluation. The participants' most emphasis was on self-care and psychological coping dimensions. These findings can be used as a basis for educational interventions toward IBD patients' empowerment. More researches are needed to explore factors affecting the empowerment processes of IBD patients.

Photobiomodulation therapy compensate the impairments of diabetic bone marrow mesenchymal stem cells.

Pathophysiologic conditions associated with diabetes mellitus affect mesenchymal stem cells (MSCs), and this phenomenon may lead to some diabetic secondary complications. The present study was conducted to evaluate the impact of photobiomodulation (PBM) on rat diabetic MSC (DMSC) behavior in vitro. For the purpose of PBM, we used helium-neon laser with a wavelength of 632.8 nm at three different energy densities (0.5, 1, 2 J/cm2) and radiation periodicity of once, twice, and thrice. The survival, proliferation, and apoptosis in the normal MSCs (NMSCs), DMSCs, and diabetic MSCs, which were laser irradiated (DMSCs+L), were assessed using MTT assay, Ki67 immunofluorescence staining, and TUNEL assay, respectively. Our results demonstrated that DMSCs have significantly lower survival (P < 0.05) and proliferation rates (P < 0.001), and dramatically higher population doubling time (PDT, P < 0.001) and apoptosis rates (P < 0.001) as compared to NMSCs. Moreover, PBM with energy density of 1 J/cm2 and the periodicity of 1 or 2 times could improve diabetic MSC capabilities in the term of survival, proliferation, and apoptosis. Considering these findings, it is suggested that PBM could improve the ability of diabetic MSCs in vitro prior to transplantation or may rise their capabilities in their native niche in vivo.

The associations between dietary patterns and bone health, according to the TGF-ß1 T869→C polymorphism, in postmenopausal Iranian women.

BACKGROUND/OBJECTIVE: Recent studies have shown that dietary variants and genetic variants play a decisive role in the risk of developing osteoporosis. Therefore, the objective of the present study was to examine associations between dietary pattern and bone health, according to the TGF-ß1 T869→C polymorphism, in postmenopausal Iranian women. MATERIALS AND METHODS: In this study, 264 postmenopausal women aged from 46 to 78 years were examined. Body composition was measured by a body composition analyzer and physical activity by the short-form physical activity questionnaire. Bone mineral density was measured by the DEXA method. Dietary patterns were determined using factor analysis on 27 foods groups, employing a valid, reliable 147-item semi-quantitative food frequency questionnaire. The dietary patterns were analyzed by the factor analysis method. Blood samples were taken for measuring blood parameters. DNA samples from participants were genotyped using the RFLP-PCR method. RESULTS: Three dietary patterns were identified, namely: mediterranean diet, traditional diet, and unhealthy diet-one of which was associated with bone health. Postmenopausal women following a Mediterranean diet had lower weight and central obesity (0.05 > P). Higher adherence to a Mediterranean pattern was positively associated with Z-score L2_L4 lumbar spine (0.05 > P). TGF-ß1 T869→C genotypes, after adjustment, were not directly correlated with bone mineral density and body composition (0.05 < P). Moreover, these findings demonstrated that in participants adhering to a Traditional dietary pattern, the C allele carrier group (TC and CC genotypes) had a lower L2_L4 Z-score (P = 0.05). CONCLUSION: It seems that the mediterranean diet can be a beneficial dietary pattern in the prevention of osteoporosis and obesity in postmenopausal women. Furthermore (probably in the C allele carrier group), lower vitamin D intake, coupled with adherence to a traditional dietary pattern, reduces the deposition of TGF-beta and increases the risk of lumbar spine osteoporosis.

Effect of drying methods on the structure, thermo and functional properties of fenugreek (Trigonella foenum graecum) protein isolate.

BACKGROUND: Different drying methods due to protein denaturation could alter the functional properties of proteins, as well as their structure. So, this study focused on the effect of different drying methods on amino acid content, thermo and functional properties, and protein structure of fenugreek protein isolate. RESULTS: Freeze and spray drying methods resulted in comparable protein solubility, dynamic surface and interfacial tensions, foaming and emulsifying properties except for emulsion stability. Vacuum oven drying promoted emulsion stability, surface hydrophobicity and viscosity of fenugreek protein isolate at the expanse of its protein solubility. Vacuum oven process caused a higher level of Maillard reaction followed by the spray drying process, which was confirmed by the lower amount of lysine content and less lightness, also more browning intensity. ΔH of fenugreek protein isolates was higher than soy protein isolate, which confirmed the presence of more ordered structures. Also, the bands which are attributed to the α-helix structures in the FTIR spectrum were in the shorter wave number region for freeze and spray dried fenugreek protein isolates that show more possibility of such structures. CONCLUSION: This research suggests that any drying method must be conducted in its gentle state in order to sustain native structure of proteins and promote their functionalities. © 2017 Society of Chemical Industry.

Fenugreek (Trigonella foenum graecum) seed protein isolate: extraction optimization, amino acid composition, thermo and functional properties.

BACKGROUND: With increasing demand for new protein sources, research on plant protein extraction and evaluation of the functional properties of protein isolates is necessary. In this study, pH and NaCl concentration, as two parameters affecting protein extraction of fenugreek seed, was investigated and the condition of fenugreek protein isolate (FPI) extraction was optimized using response surface methodology. RESULTS: FPI had significantly (P< 0.05) higher protein and essential amino acid content (891.00 and 387.41 g kg(-1) , respectively) compared with soy protein isolate (SPI). FPI was rich in Asp and Glu, confirming the presence of bands in the acidic region (30-39 kDa) of its electrophoretic pattern. Differential scanning calorimeter thermography of both FPI and SPI showed two peaks with high denaturation temperature, confirming the presence of high protein content and hydrophobic amino acids. Protein solubility, foaming capacity, foam stability and emulsion stability of FPI were higher than SPI; moreover, both FPI and SPI showed pH-dependent protein functionalities. CONCLUSION: Fenugreek seed protein extraction was optimized by control of pH and NaCl concentration. FPI could be used as a protein source with remarkable functional properties.

Enhanced differentiation of mesenchymal stem cells in coral-incorporated PCL/elastin scaffold enables 3D defect healing in osteoporosis rat model.

In osteoporosis, bone quality adversely affects the tissue structural competence which increases the risk of a complicated fracture healing. In the present study highly potent scaffold containing natural coral particles was designed and considered for the healing of critical size bone defect in osteoporosis rat model. Scaffold morphological evaluation confirmed the porous nanofibrous structure. Water uptake of about 900 % was obtained for the fabricated scaffold as the result of its composition and three-dimensional structure. Mechanical analysis revealed the compressive modulus of about 50 kPa for the fabricated coral-incorporated nanofibrous structure. In vitro cellular assessments revealed that the designed scaffold induces no toxicity and provides the proper substrate for cell attachment together with increased and prolonged cell proliferation. In vivo experiments demonstrated that implantation of the fabricated scaffold in the femoral defects of osteoporotic rats significantly increased the number of osteocytes and osteoblasts, and enhanced the BTV, and BMP-2 expression compared with the control group. Furthermore, it was observed that seeding the scaffolds with MSCs prior to implantation, resulted in substantial improvements in mRNA expression of the BMP-2 and VEGF genes and considerable enhancement in stereological findings such as significantly higher number of osteoblasts, osteocytes, TVB, and BTV.

Systematic review with meta-analysis: Steatosis severity and subclinical atherosclerosis in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver condition recognised as an independent risk factor for cardiovascular disease (CVD). However, there is ongoing debate regarding the effective strategy for cardiovascular risk assessment in MASLD. AIM: To investigate the relationship between liver imaging, specifically focusing on the severity of steatosis and subclinical atherosclerosis. METHODS: We conducted a thorough search across four databases, from 1950 to April 2023, to identify eligible studies employing imaging to explore the relationship between different degrees of steatosis and subclinical atherosclerosis among MASLD. Additionally, we conducted a quality assessment using the Newcastle Ottawa Scale, performed a meta-analysis employing the DerSimonian-Liard random-effects model, and conducted subgroup analyses for validation. RESULTS: In total, 19 studies, encompassing 147,411 middle-aged individuals without previous CVD (74.94% male; mean age 45.53 years [SD 10.69]; mean BMI 24.3 kg/m2 [SD 3.35]), were included. The pooled odds ratio for subclinical atherosclerosis was 1.27 (95% CI: 1.13-1.41, I2 = 76.68%) in mild steatosis and significantly increased to 1.68 (95% CI: 1.41-2.00, I2 = 89.02%) in moderate to severe steatosis. Sensitivity analysis, focusing on high-quality studies, consistently supported this finding and the results remained robust across subgroup analyses. Furthermore, meta-regression revealed that a higher mean AST and ALT, alongside a lower mean HDL, were significant moderators of this association. CONCLUSIONS: Even mild steatosis is associated with CVD risk, and steatosis severity further intensifies this association. These findings suggest that liver fat quantification enhances CVD risk stratification in patients with MASLD.

Association of oxytocin augmentation with postpartum hemorrhage: a systematic review and meta-analysis.

OBJECTIVE: The current study aims to evaluate the correlation between oxytocin augmentation and postpartum hemorrhage. METHOD: PubMed, Web of Science, and Scopus has been searched for studies assessing the correlation between oxytocin augmentation and postpartum hemorrhage up to January 24, 2024. The search strategy included relevant keywords related to PPH and oxytocin augmentation. The risk of bias assessment was conducted by two reviewers using the Newcastle-Ottawa Scale (NOS). To pool the effects sized of included studies odds ratios (OR) of interest outcome with their 95% confidence interval (CI) were used. RESULTS: Eight studies were included in this meta-analysis. The pooled analysis of the included studies showed a statistically significant association between oxytocin augmentation and increased odds of PPH (pooled odds ratio [OR] = 1.27, 95% confidence interval [CI]: 1.05-1.53; I2 = 84.94%; p = 0.01). Publication bias was assessed using funnel plots, which appeared relatively asymmetrical, indicating significant publication bias. Galbraith plot and trim and fill plot were used for publication bias. Sensitivity analyses were performed by leave one out method. CONCLUSION: This meta-analysis suggests that using oxytocin for labor augmentation is linked to a significant increase in the risk of PPH. It highlights the need for careful monitoring and consideration when using oxytocin, especially in low and middle-income countries where guidelines and supervision are crucial.

Building Digital Twins for Cardiovascular Health: From Principles to Clinical Impact.

The past several decades have seen rapid advances in diagnosis and treatment of cardiovascular diseases and stroke, enabled by technological breakthroughs in imaging, genomics, and physiological monitoring, coupled with therapeutic interventions. We now face the challenge of how to (1) rapidly process large, complex multimodal and multiscale medical measurements; (2) map all available data streams to the trajectories of disease states over the patient's lifetime; and (3) apply this information for optimal clinical interventions and outcomes. Here we review new advances that may address these challenges using digital twin technology to fulfill the promise of personalized cardiovascular medical practice. Rooted in engineering mechanics and manufacturing, the digital twin is a virtual representation engineered to model and simulate its physical counterpart. Recent breakthroughs in scientific computation, artificial intelligence, and sensor technology have enabled rapid bidirectional interactions between the virtual-physical counterparts with measurements of the physical twin that inform and improve its virtual twin, which in turn provide updated virtual projections of disease trajectories and anticipated clinical outcomes. Verification, validation, and uncertainty quantification builds confidence and trust by clinicians and patients in the digital twin and establishes boundaries for the use of simulations in cardiovascular medicine. Mechanistic physiological models form the fundamental building blocks of the personalized digital twin that continuously forecast optimal management of cardiovascular health using individualized data streams. We present exemplars from the existing body of literature pertaining to mechanistic model development for cardiovascular dynamics and summarize existing technical challenges and opportunities pertaining to the foundation of a digital twin.