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Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents to address these defects. In this review, we provide an overview and prospect of the new antibacterial agents that can be used or have the potential to be applied in bone cement, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides and enzymes. Additionally, we have conducted a preliminary assessment of the feasibility of bone cement containing N-halamine, which has demonstrated good antibacterial activities. The conclusion of this review is that the research and utilization of bone cement containing novel antibacterial agents contribute to addressing the limitations of ALBCs. Therefore, it is necessary to continue expanding the research and use of bone cement incorporating novel antibacterial agents. This review offers a novel perspectives for designing ABCs and treating bone infections. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the independent and joint associations of vitamin B12 and methylmalonic acid (MMA) with all-cause, cardiovascular disease (CVD), and cancer mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: We included 6797 individuals with MASLD from the U.S. National Health and Nutrition Examination Survey. Serum MMA was measured using gas/liquid chromatography-mass spectrometry. Serum vitamin B12 was measured using commercial kits. The separate and joint associations of dietary intake and serum vitamin B12 (cutoff: 400 pg/mL) and MMA (cutoff: 250 nmol/L) levels with mortality were assessed by Cox proportional hazards regression. Results: During a median follow-up of 9.3 years, 1604 deaths were documented, including 438 from CVD and 365 from cancer. In MASLD patients, dietary intake and serum vitamin B12 did not associate with mortality, while MMA was associated with a 1.35-fold increased risk of all-cause mortality (P-trend < 0.001). The adjusted hazard ratios for the joint association of vitamin B12 and MMA with all-cause and CVD mortality were 1 in the B12lowMMAlow group (reference), 1.02 (0.87–1.20) and 1.15 (0.90–1.47) in the B12highMMAlow group, 1.55 (1.29–1.86) and 1.84 (1.28–2.65) in the B12lowMMAhigh group, and 1.82 (1.49–2.21) and 2.28 (1.40–3.71) in the B12highMMAhigh group, respectively. The joint association was modified by serum folate (P-interaction = 0.001). Conclusions: In MASLD patients, MMA rather than dietary and serum vitamin B12 was positively associated with all-cause mortality. The joint effect of high levels of MMA and vitamin B12 showed the strongest associations with all-cause and CVD mortality, with a significant interaction with serum folate. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the shear bond strength (SBS) of repair material to conventionally, subtractive‐, and additive‐manufactured denture bases after different surface treatments. Materials and Methods: Disk‐shaped test specimens (N = 300) were prepared from denture base materials produced by one conventional (Procryla), one subtractive (Yamahachi), and one additive (Curo Denture) method. The test specimens were randomly divided into five groups (n = 10) and exposed to a variety of surface treatments—Group A: no surface treatment; Group B: grinding with silicon carbide paper; Group C: sandblasting; Group D: erbium: yttrium‐aluminum‐garnet laser; and Group E: plasma. Repair was performed with autopolymerizing acrylic resin (Meliodent). Surface roughness analyses were performed with a profilometer. Scanning electron microscopy was used to examine one specimen from each subgroup. SBS was evaluated on a universal testing machine. Failure types were observed under a stereomicroscope. Results: Surface roughness values were significantly higher in all test materials in Group D than in the other groups (p < 0.001). For conventional resin, the SBS values were higher in Group C than in Groups A, D, and E (p < 0.001). For CAD/CAM material, Groups B and C had significantly greater SBS increases compared with Group E (p < 0.001). For 3D material, Group D showed higher SBS than all groups except Group C (p < 0.001). Conclusions: For SBS, sandblasting was most effective in the conventional group, whereas laser treatment was the most effective in the additive‐manufactured group. For the subtractive group, surface treatments other than plasma exhibited similar SBS. Clinical Significance: In repairing fractured prostheses, any degree of roughening suitable for the material content may provide an SBS benefit. [ABSTRACT FROM AUTHOR]

Objective: Clinicians have noted that the ongoing war on Gaza has had a psychological impact on people with multiple sclerosis (PwMS) whose mental health is particularly vulnerable during stressful times such as these. The present study sought to examine the prevalence and correlates of posttraumatic stress disorder (PTSD) symptoms among PwMS in Jordan during the Gaza war outbreak. Methods: This was a cross-sectional study involving 171 patients (PwMS) out of 372 patients approached (46% response rate) who were being seen in the MS unit at Al Bashir Hospital, Ammann, Jordan. Inclusion criteria required that participants had been following daily news updates of the October 7 war in Gaza during a period of 4 months. Results: Of participants, 125 (73.1%) were female, 98 (57.3%) were on therapy for less than five years, and 30 (17.5%) reported having a relapse during the past 6 months. Significant PTSD symptoms were identified in 58.5% (100 of 171 participants). Those at higher risk were the unemployed (OR = 2.14, 95% CI = 1.13-4.07, P = 0.02), whereas patients receiving dimethyl fumarate (19.9%) were at lower risk (OR = 0.43, 95% CI = 0.19-0.94, P = 0.02). Conclusion: The high rate of significant PTSD symptoms among people with MS in this study underscores the need for attention by primary care providers and the implementation of a comprehensive multidisciplinary approach to optimize the mental well-being of this fragile population. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the bioavailability of vitamin B12 from nori and to evaluate the required dosage for improving vitamin B12 nutritional status in vegetarians not using supplements. Methods: The study design is an open-label, parallel, dose-response randomized controlled trial. Thirty vegetarians were assigned to control (no nori), low-dose (5 g nori, aiming to provide 2.4 µg vitamin B12 per day), or high-dose (8 g nori, aiming to provide 4 µg vitamin B12 per day) groups. The primary outcome was changes in vitamin B12 status as measured by serum vitamin B12, holotranscobalamin (holoTC), homocysteine (Hcy), and methylmalonic acid (MMA), and a combined score of these four markers (4cB12 score) during the four-week intervention. Dietary vitamin B12 intakes were assessed at baseline and end of the trial with a 17-item food frequency questionnaire designed for vitamin B12 assessment. General linear model was used to compare least square means of changes in each biomarker of vitamin B12 status, among the three groups, while adjusting for respective baseline biomarker. Results: After adjusting for baseline status, nori consumption led to significant improvement in serum vitamin B12 (among-group P-value = 0.0029), holoTC (P = 0.0127), Hcy (P = 0.0225), and 4cB12 (P = 0.0094). Changes in MMA did not differ significantly across groups, but showed within-group pre-post improvement in the low-dose group (median [p25, p75] = -339 [-461, -198] nmol/L). Vitamin B12 status appeared to plateau at low dose (5 g of nori), which compared with control group, improved serum vitamin B12 (lease square mean [95% CI] = + 59 [25, 93] pmol/L, P = 0.0014); holoTC (+ 28.2 [10.1, 46.3] pmol/L, P = 0.0035); Hcy (-3.7 [-6.8, -0.6] µmol/L, p = 0.0226); and 4cB12 score (+ 0.67 [0.24, 1.09], p = 0.0036). High-dose resulted in similar improvements. There was no significant difference between low-dose and high-dose groups in all biomarkers of vitamin B12. Conclusions: Consuming 5 g of nori per day for 4 weeks significantly improved vitamin B12 status in vegetarians. A higher dose (8 g) may not confer additional benefits. Clinical trial registration: ClinicalTrials.gov Identifier: NCT05614960. Date of registration: November 14th 2022. [ABSTRACT FROM AUTHOR]

Purpose: Several preliminary studies suggest dietary guanidinoacetic acid (GAA) might impact methyl group availability and/or methylation biomarkers, fueling ongoing debates. This study aimed to explore the relationship between dietary GAA intake and plasma indicators of the methylation cycle in individuals aged one year and older, using data from the 2001–2002 National Health and Nutrition Examination Survey (NHANES). Methods: Dietary information was obtained from individuals who completed a 24-hour Dietary Recall, with total daily intake of GAA calculated by aggregating all relevant food items. Relevant variables related to the methylation cycle, such as red blood cell (RBC) folate and serum folate, vitamin B12, total homocysteine (tHCy), and methylmalonic acid (MMA), were identified from the NHANES 2001–2002 laboratory assessments. Results: A total of 9,115 individuals (51.3% females) were included in the final analysis. Linear regression unveiled a significant association between higher GAA intake and diminished RBC folate (p < 0.001), serum folate (p < 0.001), and MMA levels (p = 0.007). It also revealed an elevation in tHCy levels with increased GAA intake (p < 0.001). These associations remained significant even after adjusting for demographic variables and dietary factors pertinent to the methylation cycle (p < 0.05). Conclusion: Our findings suggest that dietary exposure to GAA (resulting in conversion to creatine) could be considered a nutritional factor associated with the consumption of methyl groups in the general population. [ABSTRACT FROM AUTHOR]

Background: Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. Methods: GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. Results: The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). Conclusions: The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect of neutral 10-methacryloyloxydecyl dihydrogen phosphate salt (MDP-Na) on the dentin bond strength and remineralization potential of etch-&-rinse adhesive. Methods: Two experimental etch-&-rinse adhesives were formulated by incorporating 0 wt% (E0) or 20 wt% (E20) neutral MDP-Na into a basic primer. A commercial adhesive, Adper Single Bond 2 (SB, 3 M ESPE), served as the control. Sixty prepared teeth were randomly allocated into three groups (n = 20) and bonded using either one of the experimental adhesives or SB. Following 24 h of water storage, the bonded specimens were sectioned into resin-dentin sticks, with four resin-dentin sticks obtained from each tooth for microtensile bond strength (MTBS) test. Half of the sticks from each group were immediately subjected to tensile loading using a microtensile tester at a crosshead speed of 1 mm/min, while the other half underwent tensile loading after 6-month incubation in artificial saliva (AS). The degree of conversion (DC) of both the control and experimental adhesives (n = 6 in each group) and the adsorption properties of MDP-Na on the dentin organic matrix (n = 5 in each group) were determined using Fourier-transform infrared spectrometry. Furthermore, the effectiveness of neutral MDP-Na in promoting the mineralization of two-dimensional collagen fibrils and the adhesive-dentin interface was explored using transmission electron microscopy and selected-area electron diffraction. Two- and one-way ANOVA was employed to assess the impact of adhesive type and water storage on dentin bond strength and the DC (α = 0.05). Results: The addition of MDP-Na into the primer increased both the short- and long-term MTBS of the experimental adhesives (p = 0.00). No difference was noted in the DC between the control, E0 and E20 groups (p = 0.366). The MDP-Na remained absorbed on the demineralized dentin even after thorough rinsing. The intra- and extra-fibrillar mineralization of the two-dimensional collagen fibril and dentin bond hybrid layer was confirmed by transmission electron microscopy and selected-area electron diffraction when the primer was added with MDP-Na. Conclusions: The use of neutral MDP-Na results in high-quality hybrid layer that increase the dentin bond strength of etch-&-rinse adhesive and provides the adhesive with remineralizing capability. This approach may represent a suitable bonding strategy for improving the dentin bond strength and durability of etch-&-rinse adhesive. [ABSTRACT FROM AUTHOR]

Epilepsy can be caused by a variety of causes, such as inborn errors of metabolism, organic acid disorders are the most significant type of metabolic disorders that cause seizures. The clinical manifestations of these diseases are generally nonspecific, and the types of seizures are different. Screening for multisystem clinical symptoms and identifying the underlying etiology are crucial for early treatment of epileptic seizures. This article provides a comprehensive summary of the pathogenesis, clinical features, diagnosis and treatment of epilepsy associated with organic acid metabolism disorders. Furthermore, relevant literature has also been reviewed to assist clinicians in the diagnosis of cases characterized by the coexistence of multisystemic symptoms and epileptic manifestations. [ABSTRACT FROM AUTHOR]

In this study, we retrospectively analysed the efficacy and safety of three treatment models, namely, short-course radiotherapy sequential XELOX chemotherapy, neoadjuvant mFOLFOX6 concurrent radiotherapy and long-course concurrent radiotherapy with total mesorectal excision (TME) after treatment of locally advanced rectal cancer with high-risk factors. We collected clinical data on 177 patients with locally advanced rectal cancer (cT3-4 and/or cN+) who were treated at the Department of Abdominal Oncology of the Affiliated Cancer Hospital of Guizhou Medical University from December 2017 to December 2022. All patients were associated with 2-3 risk factors [T4b, N2, Extramural Vascular Invasion (EMVI), Mesorectal Fascia (MRF) positivity], positive lateral lymph nodes. Among them, there were 45 cases in the short course radiotherapy sequential XELOX chemotherapy group (RT + XELOX group); 64 cases in the neoadjuvant mFOLFOX6 concurrent radiotherapy group (mFOLFOX6 + CRT group); and 68 cases in the long course concurrent radiotherapy group (CRT group). The RT + XELOX group and mFOLFOX6 + CRT group completed radiotherapy and 4 cycles of neoadjuvant chemotherapy, respectively, and then rested for 1-2 weeks before TME surgery; the CRT group completed concurrent radiotherapy and then rested for 6-8 weeks before TME surgery.Adjuvant chemotherapy was conducted after surgery in each of the three groups: 2 cycles of adjuvant chemotherapy with XELOX regimen in the RT + XELOX group, 4-6 cycles of adjuvant chemotherapy with mFOLFOX6 in the mFOLFOX6 + CRT group, and 8-12 cycles of adjuvant chemotherapy with mFOLFOX6 in the CRT group.The pathological complete response rate (pCR rate), tumour downstage rate, tumour complete resection rate (R0 resection rate), local recurrence rate, distant metastasis rate, overall survival rate, incidence of adverse reactions, surgical complications and completion rate of perioperative systemic chemotherapy were compared among patients in the three groups of cases after TME. The pCR rate (21.95% vs 17.24% vs 5.00%, p = 0.034) and and tumour downstage rate (78.05% vs 68.97% vs 53.33%, p = 0.029) were higher in the RT + XELOX group and mFOLFOX6 + CRT group compared to the CRT group. The RT + XELOX group had a lower 3-year distant metastasis rate (14.63% vs 36.67%, p = 0.048) and improved 3-year overall survival (76.57% vs 48.56%, p < 0.001) compared to the CRT group. There was no significant reduction in the 3-year distant metastasis rate in the mFOLFOX6 + CRT group versus the CRT group (27.59% vs 36.67%, p = 0.719), and the 3-year overall survival was similar (51.23% vs 48.56%, p = 0.35). Multi-logistic regression analysis and stratified analysis showed that patients in the RT + XELOX group and mFOLFOX6 + CRT group were more likely to achieve pCR than the CRT group (RT + XELOX group: OR 7.3, 95% CI [2.6-20.8], p < 0.001; mFOLFOX6 + CRT group OR 2.9, 95% CI [1.1-7.9], p = 0.036). The completion rates of perioperative systemic chemotherapy in the RT + XELOX, mFOLFOX6 + CRT, and CRT groups were 82.93% vs. 84.48% vs. 61.67% (χ2=9.95, p = 0.007), respectively. And there were significant differences in grade 3-4 leukopenia and thrombocytopenia (incidence of leukopenia: 15.50% vs. 7.81% vs. 1.47%, p = 0.045; incidence of thrombocytopenia: 13.33% vs 7.81% vs 1.47%, p = 0.027). There was no significant difference in the incidence of intraoperative and postoperative complications among the three groups (p > 0.05). RT + XELOX group and mFOLFOX6 + CRT group significantly improved the near-term outcome (e.g., pCR rate) in patients with locally advanced rectal cancer with high-risk factors compared with CRT group. The RT + XELOX group also reduced the 3-year distant metastasis rate, increased the 3-year overall survival rate, and did not increase the incidence of perioperative surgical complications. It provides an effective means for the comprehensive treatment of locally advanced rectal cancer and has important clinical guidance and application value. [ABSTRACT FROM AUTHOR]

Background: Remimazolam is a relatively new benzodiazepine with growing use in procedural sedation and general anaesthesia. Initiated by case reports, the physical incompatibility of remimazolam with ringer's acetated and ringer's lactated solution has been reported. More recently, remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam, have been investigated and suggested safe for coadministration with remimazolam. Apart from case reports, incompatibility for other frequently used drugs remains unknown. Methods: Sixty-five drugs and intravenous fluids were tested for possible precipitation with remimazolam in a simulated y-site administration. Equal volumes of the test drug were injected into the remimazolam solution, examined and photo documented at 1, 15, 30 and 60 min after mixture. Examination was taken by two independent investigators. pH was measured before, and 60 min after mixing the drugs. Results: Seventeen (26.15%) drugs or fluids showed precipitation, 47 (72.31%) did not show any sign of interaction. Propofol could not be assessed, because of the turbidity of the substance itself. Precipitation occurred immediately and remained stable in all timestamps. The incompatible drug-remimazolam-mixtures had a median pH of 7.15 (6.67, 8.01), the non-precipitating mixtures a median pH of 4.75 (3.8, 5.6). The pH-values of both groups were significantly different (Mann-Whitney-U-test; p <.00001). There is an increasing risk for precipitation with more basic baseline pH-levels of the tested drug. No interaction was seen in baseline pH below 5. Conclusions: Remimazolam (Byfavo®) is incompatible with ampicillin/ sulbactam, calcium gluconate, clindamycin, dexamethasone, dimenhydrinate, an 148mval/l electrolyte - glucose 1% solution (E148G1®), furosemide, a 4% gelatine volume expander (gelafundin®), heparin sodium, insulin, meropenem, sodium bicarbonate 8.4%, prednisolone, the crystalloid infusions jonosteril® and sterofundin®, thiopental and tranexamic acid. The results strongly affirm remimazolam's safety requirements: A separate line for remimazolam and an approved compatible baseline infusion is mandatory and an alternative way to administer bolus medication is required. [ABSTRACT FROM AUTHOR]

Wolff-Parkinson-White (WPW) syndrome is a rare cardiac condition arising from abnormal embryologic development of the annulus fibrosus in combination with the cardiac conduction system. The abnormality results in the development of accessory pathways and preexcitation changes which can provoke episodes of tachyarrhythmias. The most common presentation of WPW syndrome is supraventricular tachycardia. Beyond customary abortive therapy, chronic management strategies vary based upon timing and clinical severity of the initial disease presentation. Prompt diagnosis and rate control have a dramatic impact on the outcomes of morbidity and mortality. The purpose of this article is to present a case study of a preterm infant who manifested with WPW syndrome. Additionally, the article will explore the pathophysiology of WPW syndrome and the timing and presentation of common clinical manifestations of the disease, along with current diagnostic and treatment strategies to achieve optimal patient outcomes in the neonatal population. [ABSTRACT FROM AUTHOR]

Givinostat (DUVYZAT™), an orally available histone deacetylase inhibitor, is being developed by Italfarmaco for the treatment of muscular dystrophy and polycythemia vera. Givinostat received its first approval on 21 March 2024, in the USA, for the treatment of Duchenne muscular dystrophy (DMD) in patients 6 years of age and older. Approval was based on the results of the multinational phase III EPIDYS trial, in which givinostat recipients showed less decline than placebo recipients in the time taken to perform a functional task. Givinostat represents the first nonsteroidal treatment for DMD to be approved for use in patients irrespective of the specific genetic variant underlying their disease. Givinostat is available as an oral suspension to be administered twice daily with food. The recommended dosage is based on the body weight of the patient. In the EU, regulatory review of givinostat in DMD is currently underway. This article summarizes the milestones in the development of givinostat leading to this first approval for DMD. [ABSTRACT FROM AUTHOR]

Background: In addition to other variables associated with PRP injections for Knee Osteoarthritis (OA), some confusion exists about the role of exogenous activators. The current study looks at matched groups getting PRP injections with or without activator (Calcium gluconate) in early knee OA patients. Methods: Patients of early OA knee meeting inclusion criteria were randomly divided into 2 groups; Group A (43 patients) received 8 ml PRP injection alone, and Group B (48 patients) received 8 ml PRP along with 2 ml Calcium gluconate as activator. The patients were evaluated at baseline, 6 weeks, 3 months and 6 months for WOMAC Pain and Total WOMAC scores; secondary variables assessed were VAS score and patient satisfaction. Results: The baseline characteristics of both groups were comparable. Leucocyte-depleted PRP with 5 times concentration and average absolute platelet numbers of 7.144 billion per knee was injected. Mean Pain WOMAC scores decreased in both groups from baseline (group A—8.68, group B—9.09) to final follow-up (group A—4.67, group B—5.11). Similarly, Mean Total WOMAC scores decreased from baseline (group A—37.81, group B—37.41) to (group A—21, group B—21.36) at the final follow-up in both groups. There was no significant difference between both groups, and both showed similar trends. Similar findings were noted for VAS scores. Patient satisfaction was also not different (group A, 90.69%, group B, 89.58%) at the end of 6 months. Conclusion: Our study concluded doubtful role of adding exogenous activator to PRP preparation. [ABSTRACT FROM AUTHOR]

Indium-based oxides are promising electrocatalysts for producing formate via CO2 reduction reaction, in which *OCHO is considered the key intermediate. Here, we identified that the *COOH pathway could be preferential to produce formate on In2O3 of In/In2O3 heterojunction due to the synergistic effect of oxygen species and vacancy. Specifically, *CO2 and *COOH were observed on In2O3 and related to formate production by in situ Raman spectroscopy. The theoretical calculations further demonstrated that the energy barrier of the *COOH formation on In2O3 was decreased in the presence of oxygen vacancy, similar to or lower than that of the *OCHO formation on the In surface. As a result, a formate selectivity of over 90% was obtained on prepared In/In2O3 heterojunction with 343 ± 7 mA cm-2 partial current density. Furthermore, when using a Si-based photovoltaic as an energy supplier, 10.11% solar--to--fuel energy efficiency was achieved. [ABSTRACT FROM AUTHOR]

Objectives: In order to evaluate the effect of methacrylated hyaluronic acid (HAMA) hydrogels containing the recombinant human amelogenin (rhAm) in vitro and in vivo. Background: The ultimate goal in treating periodontal disease is to control inflammation and achieve regeneration of periodontal tissues. In recent years, methacrylated hyaluronic acid (HAMA) containing recombinant human amyloid protein (rhAm) has been widely used as a new type of biomaterial in tissue engineering and regenerative medicine. However, there is a lack of comprehensive research on the periodontal regeneration effects of this hydrogel. This experiment aims to explore the application of photoresponsive recombinant human amelogenin‐loaded hyaluronic acid hydrogel for periodontal tissue regeneration and provide valuable insights into its potential use in this field. Materials and Methods: The effects of rhAm‐HAMA hydrogel on the proliferation of human periodontal ligament cells (hPDLCs) were assessed using the CCK‐8 kit. The osteogenic differentiation of hPDLCs was evaluated through ALP staining and real‐time PCR. Calvarial parietal defects were created in 4‐week‐old Sprague Dawley rats and implanted with deproteinized bovine bone matrix in different treatment groups. The animals were euthanized after 4 and 8 weeks of healing. The bone volume of the defect was observed by micro‐CT and histological analysis. Results: Stimulating hPDLCs with rhAm‐HAMA hydrogel did not significantly affect their proliferation (p >.05). ALP staining and real‐time PCR results demonstrated that the rhAm‐HAMA group exhibited a significant upregulation of osteoclastic gene expression (p <.05). Micro‐CT results revealed a significant increase in mineralized tissue volume fraction (MTV/TV%), trabecular bone number (Tb.N), and mineralized tissue density (MTD) of the bone defect area in the rhAm‐HAMA group compared to the other groups (p <.05). The results of hematoxylin and eosin staining and Masson staining at 8 weeks post‐surgery further supported the results of the micro‐CT. Conclusions: The results of this study indicate that rhAm‐HAMA hydrogel could effectively promote the osteogenic differentiation of hPDLCs and stabilize bone substitutes in the defects that enhance the bone regeneration in vivo. [ABSTRACT FROM AUTHOR]

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analysed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (FFQ) and plasma one-carbon metabolites and related B-vitamin status markers (GC–MS/MS, LC–MS/MS or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol and total energy intake. Average (geometric mean (95 % prediction interval)) intake was forty-nine (38, 63) energy percent (E%) from carbohydrate, thirty-one (22, 45) E% from fat and seventeen (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e. with higher plasma pyridoxal 5'-phosphate (PLP) (% change (95 % CI) 3·1 (2·1, 4·1)), cobalamin (2·9 (2·1, 3·7)), riboflavin (2·4 (1·1, 3·7)) and folate (2·1 (1·2, 3·1)) and lower total homocysteine (tHcy) (–1·4 (–1·9, −0·9)) and methylmalonic acid (MMA) (–1·4 (–2·0, −0·8)). Substitution analyses replacing MUFA or PUFA with SFA demonstrated higher plasma concentrations of riboflavin (5·0 (0·9, 9·3) and 3·3 (1·1, 5·6)), tHcy (2·3 (0·7, 3·8) and 1·3 (0·5, 2·2)) and MMA (2·0 (0·2, 3·9) and 1·7 (0·7, 2·7)) and lower PLP (–2·5 (–5·3, 0·3) and −2·7 (–4·2, −1·2)). In conclusion, a higher protein intake and replacing saturated with MUFA and PUFA were associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has revolutionized cancer treatment. Recent studies have suggested that the efficacy of immunotherapy can be further enhanced by the influence of gut microbiota. In this study, we aimed to investigate the impact of bacteria on the effectiveness of cancer immunotherapy by combining analysis of clinical samples with validation in animal models. Methods: In order to characterize the diversity and composition of microbiota and its relationship with response to immune checkpoint inhibitors (ICIs), 16S ribosomal RNA (rRNA) and GC–MS sequencing was performed on 71 stool samples from patients with advanced non‐small cell lung cancer (NSCLC) prior to treatment with immune checkpoint blockade (ICB). Furthermore, fecal microbiota transplantation (FMT) was performed from different patients into mice and a subcutaneous tumor model established using the Lewis lung cancer cell line to evaluate the therapeutic effect of PD‐1 on mice with varying gut microbiota. Results: The results demonstrated a significant association between elevated gut microbiota diversity and response to treatment with ICIs, p < 0.05. Faecalibacterium was markedly increased in the gut microbiota of responders (R), accompanied by increased short‐chain fatty acid (SCFA) levels, especially butanoic acid, acetic acid and hexanoic acid, p < 0.05. Additionally, FMT from R and nonresponders (NR) could promote an anticancer effect and reduce the expression of Ki‐67 cells in tumors in mice, p < 0.05. Moreover, R and NR FMT did not alter PD‐L1 expression in the tumor tissues of mice, p > 0.05. The diversity of gut microbiota consistently correlated with an optimistic prognosis in NSCLC patients with immunotherapy, which could be functionally mediated by SCFAs. Conclusion: The findings of the present study indicated that the diversity of gut microbiota and SCFAs is related to the efficacy of immunotherapy. FMT can effectively delay tumor progression, and enhance the effect of immunotherapy, thus providing evidence for improving the efficacy of immunotherapy in NSCLC patients. [ABSTRACT FROM AUTHOR]

Introduction: In the last decade, del Nido cardioplegia has been embedded in adult cardiac surgery involving CABG and aortic valve surgical procedures. We reviewed our early experience with del Nido cardioplegia in the setting of minimally invasive mitral valve surgery. Methods: Data on 120 consecutive patients operated between 03/2021 and 06/2022 were retrieved from our internal database (infective endocarditis and urgent operations were excluded). Patients were divided into two groups according to the use of Histidine-Tryptophan-Ketoglutarate or del Nido cardioplegia. A propensity match analysis was performed using thirteen preoperative and intraoperative variables. Several intraoperative data and early postoperative outcomes were investigated, including cardiac enzymes (Troponin I HS and CK-MB) measured upon arrival in the Intensive Care Unit (ICU), after 12 hours and everyday thereafter. Results: There was no difference in preoperative characteristics and surgical techniques between both unmatched and matched Histidine-Tryptophan-Ketoglutarate and del Nido populations. Patients in the del Nido group received a lower volume of cardioplegia (p < 0.001) and ultrafiltration during CPB (p < 0.001). Histidine-Tryptophan-Ketoglutarate was associated with a lower rate of post cross-clamp spontaneous defibrillation (p < 0.001) and showed a lower level of blood sodium after CPB (p < 0.001). The release of cardiac enzymes was similar between the two groups (p = 0.72). There was no difference in terms of postoperative morbidity and 30 day mortality. Conclusions: del Nido cardioplegia in the setting of minimally invasive mitral valve surgery seemed safe with acceptable myocardial protection and excellent early outcomes. [ABSTRACT FROM AUTHOR]

In contrast to the well-established enzymatic enantioselective decarboxylative protonation (EDP), the corresponding chemocatalytic reactions of acyclic malonic acid derivatives remain challenging. Herein, we developed a biomimetic EDP of α-alkyl-α-aryl malonate monoesters using a chiral 1,2-trans-diaminocyclohexane-based N-sulfonamide as an organocatalyst. The method demonstrates excellent chemical yields, good enantioselectivity, mild reaction conditions, and the generation of only CO2 as waste. [ABSTRACT FROM AUTHOR]

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity. OBJECTIVES: Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha- (hCGα) and beta-subunits (hCGβ), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex. METHODS: Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression. RESULTS: Perfluorohexane sulfonic acid (PFHxS) [hCGβ: 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: -0.09; 95% CI: -0.16, -0.02) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with hCGα and positively with hCGβ. Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with hCGβ only in Black participants (-0.23; 95% CI: -0.37, -0.09) and in participants with high school education or less (-0.14; 95% CI: -0.26, -0.02); conversely, perfluorononanoic acid (PFNA) was negatively associated with hCGα only in White participants (-0.15; 95% CI: -0.27, -0.03) and with hCGβ only in participants with a college education or greater (-0.19; 95% CI: -0.36, -0.01). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was <100%. Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with hCGα, and PFNA with h-hCG. CONCLUSIONS: Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with hCGα and hCGβ differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biological, clinical and public health significance of these findings. [ABSTRACT FROM AUTHOR]

The relevance of this study lies in the lack of reliable information on the key aspects of the molecular mechanisms of fatty hepatosis, a common mammalian disease, and its dangerous complications, such as fibrosis, cirrhosis, and hepatocellular carcinoma. These circumstances substantially complicate the prompt diagnosis of this hepatopathology and reduce the effectiveness of treatment. The metabolism of the heme derivative bilirubin is unique and inherent in the liver, which undergoes transformation due to hepatocyte enzyme systems to form neutral compounds, such as glucurono-conjugates and sulphoconjugates, which undergoes changes and requires analysis in fatty hepatosis in animals. The aim of the study was to determine the characteristic changes in the content of unconjugated bilirubin and its sulphoconjugate, glucuronide, monoglucuronide, monoglucoside, and diglucuronide in the blood, bile, and liver of rats under the modelling of fatty hepatosis and the administration of rehabilitation therapy. For this, the thin-layer chromatography method was used. It was found that under tetracycline-induced fatty hepatosis in laboratory rats, the concentration of unconjugated bilirubin in the blood decreased by 39.3%, bilirubin glucuronide by 44.4%, and the total fraction of bilirubin monoglucuronide and monoglycoside by 78.9%. Oral administration of the milk phospholipid complex in the composition of the BAS "FLP-MD" to sick animals ensured the maintenance of these indicators at the control level. The content of bilirubin glucuronide and bilirubin diglucuronide decreased in the liver tissue of the treated rats. When these animals were administered a phospholipid-containing bioadditives, the level of unconjugated bilirubin in the liver tissue increased by 22.2%, but the content of its conjugated forms decreased. The content of all the studied bilirubin fractions decreased in the bile of sick rats during self-rehabilitation. The components of the BAS "FLP-MD" in fatty hepatosis in rats did not affect the reduction of unconjugated bilirubin in bile but eliminated the inhibitory effect of the modelled pathology on the content of all conjugated forms of bilirubin. The findings can be used as biochemical markers to monitor the pigment metabolism in the development of fatty hepatosis in mammals. [ABSTRACT FROM AUTHOR]

Objective: Obtaining strong resin bonds to computer‐aided design and computer‐aided manufacturing (CAD‐CAM) resin‐based composites with dispersed fillers (CCRBCs) poses a challenge. Therefore, this study aimed to assess the effect of three universal adhesives and a two‐component silane coupling agent on the shear bond strength to three (CCRBCs). Materials and Methods: Eight hundred and sixty‐four specimens of Brilliant Crios, Lava Ultimate, and Tetric CAD were polished or grit blasted, bonded with Adhese Universal DC, One Coat 7 Universal (OC7), and Scotchbond Universal Plus Adhesive (SBU) with or without a silane primer. Shear bond strength was measured after 24 h and 10,000 thermocycles. Linear regressions were performed (α = 0.05). Results: After thermocycling, bond strengths were similar for the universal adhesives on polished Brilliant Crios and Lava Ultimate (p ≥ 0.408). Grit blasted Tetric CAD showed no significant differences (p ≥ 0.096). The silane primer had minimal impact on grit blasted Tetric CAD (p ≥ 0.384). The silane primer increased the bond strength of OC7 to Brilliant Crios (p = 0.001) but decreased the adhesion of SBU to Brilliant Crios and Lava Ultimate (p ≤ 0.018). Conclusions: Bond strength of universal adhesives varied with CCRBC type. The two‐component silane coupling agent showed mixed effects on adhesive performance. Clinical Significance: Selecting universal adhesives from the same CCRBC product line does not always guarantee superior bond strength. The efficacy of silane coupling agents differs based on the bonding substrate. [ABSTRACT FROM AUTHOR]

Constipation is one of the most common symptoms in childhood. Sodium-phosphate enemas are frequently preferred for the treatment of constipation and bowel cleansing. We present a case of a 5-year-old boy who presented to the Pediatric Emergency Department with complaints of constipation, abdominal pain, abdominal distension and vomiting; had been constipated for about two years and had poor nutrition, and received a full dose of CT enema® twice in the last 12 hours before admission to the hospital. Upon arrival at the Pediatric Emergency Department, the patient was given a pediatric fleet enema because he had dense stools according to radiographic evidence. Poisoning due to Sodium-phosphate enema was considered due to severe hyperphosphatemia and hypocalcemia in the laboratory evaluation. Rapid intravenous hydration and 1 mL/kg calcium gluconate intravenous infusion were started. Electrolytes returned to the normal range at the 14th hour of follow-up without the need for additional treatment. This case is presented to emphasize that due to the widespread use of sodium-phosphate enemas in the treatment of chronic constipation, these enemas can cause phosphate poisoning even when used in healthy patients at therapeutic doses. [ABSTRACT FROM AUTHOR]

L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive metabolic disorder that causes central nervous system dysfunction. We present the case of a 33-year-old woman with macrocephaly, developmental delay, cerebellar ataxia, pyramidal signs, and seizures. Despite typical clinical features and suggestive magnetic resonance imaging findings, the diagnosis was not made. Genetic analysis revealed a homozygous missense mutation in the L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene. Treatment with riboflavin and L-carnitine was initiated. L2HGA should be considered in the differential diagnosis, even in adults, when suggestive imaging findings are present. Early diagnosis is crucial for better outcomes. [ABSTRACT FROM AUTHOR]

Background: N-acetylcysteine (NAC) reduces the cytotoxicity and genotoxicity induced by monomers leached from dental composite resins. Herein, we investigated the effects of methacrylate-based resin cement used in dental implant restoration on apoptosis and genotoxicity, as well as the antiapoptotic and antigenotoxic capabilities of its component, NAC. Methods: The antioxidant NAC (0.1 or 1 wt.%) was experimentally incorporated into the methacrylate-based dental resin cement Premier®. The Premier® + NAC (0.1 or 1 wt.%) mixture was subsequently immersed into Dulbecco's modified Eagle's medium for 72 h, and used to treat human gingival fibroblasts (HGFs). The viability of HGFs was determined using the XTT assay. The formation of deoxyribonucleic acid (DNA) double-strand breaks (DNA-DSBs) was determined using a γ-H2AX assay. Reactive oxygen species (ROS), apoptosis, necrosis, and cell cycles were detected and analyzed using flow cytometry. Results: The eluate of Premier® significantly inhibited HGF proliferation in vitro by promoting a G1-phase cell cycle arrest, resulting in cell apoptosis. Significant ROS production and DNA-DSB induction were also found in HGFs exposed to the eluate. Incorporating NAC (1 wt.%) into Premier® was found to reduce cell cytotoxicity, the percentage of G1-phase cells, cell apoptosis, ROS production, and DNA-DSB induction. Conclusion: Incorporating NAC (1 wt.%) into methacrylate-based resin cement Premier® decreases the cell cytotoxicity, ROS production, and DNA-DSBs associated with resin use, and further offers protective effects against the early stages of cell apoptosis and G1-phase cell cycle arrest in HGFs. Overall, our in vitro results indicate that the addition of NAC into methacrylate-based resin cements may have clinically beneficial effects on the cytotoxicity and genotoxicity of these materials. [ABSTRACT FROM AUTHOR]

Background: Organophosphorus (OP) and carbamate poisoning are significant concerns in developing nations. This study evaluates the effectiveness of the ChE check mobile, a cholinesterase-rapid bedside diagnostic test, in the diagnosis and management of OP and carbamate poisoning. Materials and methods: We conducted this prospective observational study, involving patients with OP and carbamate poisoning over 1 year (June 2016 to June 2017) at a single tertiary care center. Levels of RBC cholinesterase (E-AChE), butyl cholinesterase (BChE), and various other determinants were systematically coded and analyzed. Results: The study population (n = 60) consisted primarily of males (n = 43; 71.7%), with a mean age of 30.6 (SD: 13.7) years. Monocrotophos (n = 10; 20.4%) and carbofuran (n = 4; 8.1%) were the commonest OP and carbamate compounds, respectively. The median initial atropinization dose was 10 (IQR: 0, 61.5) mg, with a median total administered atropine dose of 116 (IQR: 32, 320) mg. A significant negative correlation was found between E-AChE levels and both the initial atropinization dose (ρ: -0.653, p-value < 0.001) and total atropine requirement (ρ: -0.659, p-value < 0.001) during admission. An E-AChE cut-off of 4 units/g hemoglobin provided an area under the curve of 0.73 (sensitivity: 80.0%, specificity: 68.6%, p-value < 0.001) for predicting moderate to severe peradeniya organophosphorus poisoning. Conclusion: The check mobile device can be a valuable tool for prognosticating patients. There was a significant correlation between low E-AChE levels and the atropine requirement and severity. [ABSTRACT FROM AUTHOR]

Autologous bone grafts are currently the standard in orthopedic surgery despite limited donor sources and the prevalence of donor site morbidity. Other alternatives such as allografts are more readily available than autografts but have lower rates of graft incorporation. Here, we propose a novel graft alternative consisting of an injectable poly(propylene fumarate) (PPF) and poly(propylene fumarate-co-caprolactone) P(PF- co -CL) copolymer with a recombinant human bone morphogenetic protein-2 (rhBMP-2)/vascular epithelial growth factor (VEGF) release system accompanied by hydroxyapatite (HA). The efficacy of scaffold formulations was studied using a standard, bilateral, L-level (L5-L6) posterolateral transverse spinal fusion using New Zealand white rabbits. Rabbits were divided into 4 experimental groups: group I, negative control; group II, autograft (positive control); group III, injectable PPF scaffold with rhBMP-2/VEGF release system and HA; group IV, injectable P(PF- co -CL)scaffold with rhBMP-2/VEGF release system and HA. Spines were harvested at 6 weeks and 12 weeks after surgery, and spinal fusions were assessed using manual palpation, radiographic analysis, micro-computed tomography (μCT) assessment, and histologic analysis. Of the 4 experimental groups, the injectable P(PF- co -CL) scaffold displayed superior initial strength and faster degradation than scaffolds constructed from PPF alone and facilitated the fusion of lateral processes in the rabbit standard posterolateral spinal fusion model. The results obtained from manual palpation, radiology, and μCT showed no difference between the P(PF- co -CL) group and the PPF group. However, histologic sections showed more osteogenesis with the new injectable P(PF-co-CL) scaffold. Injectable P(PF-co-CL) polymers showed promising spine fusion abilities in rabbits after 12 weeks of posterolateral implantation. [ABSTRACT FROM AUTHOR]

Iron is the most abundant transition metal on Earth. In this study, we have demonstrated an iron nanoparticle--loaded kaolin-catalyzed cross dehydrogenative coupling (CDC) reaction via C(sp³)-H activation. We use CDC of carboxylic acids with cyclohexenes to discuss various reaction parameters such as the amount of catalyst, oxidant, reaction temperature, and time. Under optimized reaction condition, the corresponding allylic ester was obtained with good yield of (85%). Screening of substituted benzoic acids and cyclic and acyclic olefins shows broad catalytic activities. Notably, the catalyst can be easily separated from the reaction mixture via simple centrifugation and remains active over five cycles of reuse. [ABSTRACT FROM AUTHOR]

Problematic alcohol use is prevalent in Russia and is deleterious for individuals with HIV and Hepatitis C Virus (HCV). Ethyl glucuronide (EtG) and blood alcohol content (BAC) provide objective biomarkers of drinking that can be compared to self-reported alcohol use. This paper describes patterns of alcohol use measured by biomarkers and self-report along with concordance across measures. Participants were Russian women with HIV and HCV co-infection (N = 200; Mean age = 34.9) from two Saint Petersburg comprehensive HIV care centers enrolled in an alcohol reduction intervention clinical trial. Measures were: (a) urine specimen analyzed for EtG; (b) breathalyzer reading of BAC; and (c) self-reported frequency of drinking, typical number of drinks consumed, and number of standard drinks consumed in the past month. At baseline, 64.0% (n = 128) had a positive EtG (> 500 ng/mL) and 76.5% (n = 153) had a positive breathalyzer reading (non-zero reading). There was agreement between EtG and BAC (kappa = 0.66, p <.001; Phi coefficient = 0.69, p <.001); self-reported alcohol measures were positively correlated with positive EtG and BAC (p's < 0.001). There was concordance between EtG and BAC measures, which have differing alcohol detection windows. Most participants endorsed frequent drinking at high quantities, with very few reporting no alcohol consumption in the past month. Concordance between biomarkers and self-reported alcohol use suggests that underreporting of alcohol use was minimal. Results highlight the need for alcohol screening within HIV care. Implications for alcohol assessment within research and clinical contexts are discussed. [ABSTRACT FROM AUTHOR]

The interest in Smallanthus sonchifolius (yacon) has strongly resurfaced due to its multiple beneficial effects on human health. This study aimed at determining the toxicity and the chemical profile of an ethanol extract (EE) and a crude lactone mixture (CLM) of yacon leaves. Cytotoxicity and genotoxicity tests were performed by the MTT assay and the alkaline version of the comet assay respectively. The phytochemical analysis, performed by chromatographic and spectroscopy techniques, revealed the presence of nine sesquiterpene lactones (STLs) and two acyclic diterpene acids. In all cases, cell viability was inversely proportional to the extract concentration employed. The effects obtained with the highest dose of EE were significantly different from those obtained with the negative and solvent controls. Conversely, no significant differences were observed between the lowest doses of EE and controls. As for CLM, all tested doses showed statistically significant increases, as compared to negative and solvent controls. [ABSTRACT FROM AUTHOR]

Purpose. To investigate whether ADSC-derived miR-23-enriched exosomes could protect against calcium oxalate stone formation in a hyperoxaluria rat model. Methods. An ethylene glycol- (EG-) induced hyperoxaluria rat model and an in vitro model of COM-induced HK-2 cells coculturing with RAW264.7 cells were established to explore the protective mechanisms of ADSC-derived miR-23-enriched exosomes. Results. The results showed that treatment with miR-23-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that coculturing with miR-23-enriched exosomes alleviated COM-induced cell autophagy. Overexpressed miR-23 suppressed M1 macrophage polarization by inhibiting IRF1 expression. Furthermore, the predicted binding site between the IRF1 messenger RNA 3 ′ -untranslated region (3 ′ -UTR) and miR-23 was confirmed by the dual-luciferase reporter assay. Conclusion. In conclusion, our research gave the first evidence that ADSC-derived miR-23-enriched exosomes affected the polarization of M1 macrophages by directly inhibiting IRF1 and protecting against calcium oxalate stone formation in a hyperoxaluria rat model. [ABSTRACT FROM AUTHOR]

Background: Screening of herbal plants for various therapeutic properties is the hour as it shows promising activity. Scientific evidence of the pharmacological activity of the plant strengthens the traditional application of plants. Methods: Rose flowers (Rosa chinensis) were procured and grounded into a coarse powder. The DNA was isolated from rose flower and molecular identification was performed by rbcL-BF and rbcL-724R primers. Antibacterial activity was evaluated by using disc and agar diffusion methods and the anti-cancer effect of the rose flower extract (RE) was examined using MTT assay in lung cancer cell line. The mechanism of cell death induced by RE was qualitatively measured using Acridine orange/Ethidium bromide staining and Hoechst staining. GC-MS analysis was performed using GC-MS-5975C. Result: The RE showed potent antimicrobial activity against various ATCC cultures. The rose extract strongly inhibits the growth of ESBL resistant organism along with inhibition of biofilm formation in the ESBL resistant organism. The extract caused apoptotic and necrotic cell death in lung cancer cells. GC-MS analysis demonstrated the presence of several biologically active compounds such as Clindamycin, Phytol, Octanoic acid, and Stigmasterol which might be the reason for the therapeutic properties of the plant. Conclusion: This study shows the antimicrobial and biofilm inhibition activity against the clinical isolates of Klebsiella pneumonia. The study shows the cytotoxic and apoptotic activity in A549 cancer cell line. Thus, the plant may act as a potent antimicrobial drug against resistant strains. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence of the negative impacts of contemporary use insecticides on sperm concentration has increased over the last few decades; however, meta-analyses on this topic are rare. OBJECTIVES: This investigation assessed the qualitative and quantitative strength of epidemiological evidence regarding adult exposure to two classes of contemporary use insecticides—organophosphates (OPs) and 푁-methyl carbamates (NMCs)—and sperm concentration using robust and reproducible systematic review and meta-analysis methods. METHODS: Three scientific databases (PubMed, Scopus, and Web of Science), two U.S. government databases (NIOSHTIC-2 and Science.gov), and five nongovernmental organization websites were searched for relevant primary epidemiological studies published in any language through 11 August 2022. Risk of bias and strength of evidence were evaluated according to Navigation Guide systematic review methodology. Bias-adjusted standardized mean difference effect sizes were calculated and pooled using a three-level, multivariate random-effect meta-analysis model with cluster-robust variance estimation. RESULTS: Across 20 studies, 21 study populations, 42 effect sizes, and 1,774 adult men, the pooled bias-adjusted standardized mean difference in sperm concentration between adult men more- and less-exposed to OP and NMC insecticides was -0.30 (95% CI: -0.49, -0.10; 푃Satt < 0.01). Sensitivity and subgroup analyses explored statistical heterogeneity and validated the model robustness. Although the pooled effect estimate was modified by risk of bias, insecticide class, exposure setting, and recruitment setting, it remained negative in direction across all meta-analyses. The body of evidence was rated to be of moderate quality, with sufficient evidence of an association between higher adult OP and NMC insecticide exposure and lower sperm concentration. DISCUSSION: This comprehensive investigation found sufficient evidence of an association between higher OP and NMC insecticide exposure and lower sperm concentration in adults. Although additional cohort studies can be beneficial to fill data gaps, the strength of evidence warrants reducing exposure to OP and NMC insecticides now to prevent continued male reproductive harm. [ABSTRACT FROM AUTHOR]

Aims Phosphatidylethanol (PEth) is only formed when ethanol is present in blood. This direct alcohol marker has been widely discussed, including the minimum amount of ethanol being necessary to form as much PEth as to exceed the threshold of 20 ng/mL in previously PEth negative subjects. In order to corroborate hitherto existing results, a drinking study including 18 participants after a 3-week alcohol abstinence was performed. Methods They consumed a pre-calculated amount of ethanol to reach a blood alcohol concentration (BAC) of at least 0.6 g/kg. Blood was drawn before and periodically seven times after alcohol administration on day 1. Blood and urine were also collected the next morning. Dried blood spots (DBS) were prepared immediately from collected venous blood. BAC was determined by head space gas chromatography and the concentrations of both PEth (16:0/18:1, 16:0/18:2 and five additional homologues) and ethyl glucuronide (EtG) were analysed using liquid chromatography–tandem mass spectrometry. Results Out of 18, 5 participants had concentrations of PEth 16:0/18:1 above the threshold of 20 ng/mL, and 11 out of the 18 subjects had concentrations between 10 and 20 ng/mL. In addition, four persons had PEth 16:0/18:2 concentrations above 20 ng/mL the following morning. All test subjects tested positive for EtG in DBS (≥ 3 ng/mL) and urine (≥100 ng/mL) upon 20–21 h after alcohol administration. Conclusion By combining both a lower cutoff of 10 ng/mL and the homologue PEth 16:0/18:2, the sensitivity to detect a single alcohol intake after a 3-week abstinence increases to 72.2%. [ABSTRACT FROM AUTHOR]

Background. Kidney stone disease induces chronic renal insufficiency by crystal-induced renal tubular epithelial cell injury. It has been reported that the prevalence of kidney stone disease is increasing, accompanied by the high recurrence rate. Alkaline mineral water has been reported to possess beneficial effects to attenuate inflammation. Here, we explored the potential protective effects and underlying mechanisms of alkaline mineral water against calcium oxalate-induced kidney injury. Methods. We performed the mice kidney stone model by administering glyoxylate at 100 mg/kg once daily for 7 days. To assess the effects of alkaline mineral water on oxalate-induced kidney injury, mice drank different water (distilled water, natural mineral water at pH = 8.0, as well as natural mineral water at pH = 9.3) for 7 days, respectively, followed by glyoxylate exposure. After collection, crystal formation, kidney injury and cell apoptosis, fibrosis, oxidative stress, as well as inflammation were measured. Results. Our results showed that glyoxylate treatment led to kidney crystal formation and fibrosis, which can be attenuated by drinking alkaline mineral water. Furthermore, alkaline mineral water also reduced kidney injury and cell apoptosis, oxidative stress, and inflammation. Conclusion. Alkaline mineral water supplement prevents progression of glyoxylate-induced kidney stones through alleviating oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: The management of vitamin B12 deficiency in patients who underwent total gastrectomy remains unclear. This study evaluated the effect of vitamin B12 replacement intervals on the clinical symptoms and laboratory findings in gastric cancer patients with vitamin B12 deficiency after total gastrectomy. The vitamin B12 levels after replacement were significantly higher in the regular replacement group than in the lab-based replacement group. The post-replacement serum hemoglobin levels and symptoms were comparable between the two groups. The management of patients with vitamin B12 deficiency after total gastrectomy (TG) remains controversial. We aimed to evaluate the effect of vitamin B12 replacement intervals on the clinical characteristics in these patients. The data from patients who received vitamin B12 supplementation after TG between 2007 and 2018 at the National Cancer Center, Korea, were retrospectively evaluated. Vitamin B12 deficiency was defined as a serum vitamin B12 level of <200 pg/mL or urine methylmalonic acid level > 3.8 mg/gCr. The patients were divided into a regular replacement group (patients received an intramuscular injection or oral medication regularly), and a lab-based replacement group (patients received vitamin B12 intermittently after checking the level). The symptoms and biochemical parameters were compared between these groups. The regular and lab-based replacement groups included 190 and 216 patients, respectively. The median vitamin B12 replacement intervals were 1 and 9 months, respectively (p < 0.001). After replacement, the regular replacement group had higher vitamin B12 levels than the lab-based replacement group (p < 0.001). However, the serum hemoglobin level showed no significant changes. After replacement, there was no significant difference in the proportion of the symptomatic patients between the groups. Replacing vitamin B12 with a lab-based protocol may be sufficient for TG patients. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal cholestasis refers to conjugated hyperbilirubinemia that either presents at birth or develops within the first three months of life. The causes of neonatal cholestasis are extensive and can be classified based on the anatomical location of the pathology into extrahepatic and intrahepatic causes This study aimed to assess the frequency and underlying etiologies of neonatal cholestasis in a tertiary care center in Jordan. Material and methods: We retrospectively reviewed the medical records of infants diagnosed with neonatal cholestasis during the study period. Demographic data, clinical presentations, laboratory results, imaging studies, and liver biopsies were collected and analyzed. Data were presented as percentages and averages. Results: Of the 47 patients diagnosed with neonatal cholestasis, 55.3% were male, and the average age at presentation was 16.7 days. Jaundice was the most common clinical feature (100%), followed by clay-colored stools and dark urine (29.7%). Notably, 12.8% of patients had skeletal abnormalities. At presentation, the average total and direct bilirubin levels were 14.3 mg/dl (± SD 7.3 mg/dl) and 10.1 mg/dl (± SD 6.5 mg/dl), respectively. Abnormal liver ultrasound findings were observed in 8 patients (17%). In our cohort, metabolic and genetic disorders were the most common underlying causes of neonatal cholestasis, followed by extrahepatic anatomical biliary disorders. Conclusions: Causes of neonatal cholestasis vary depending on the population. Metabolic and genetic disorders were the leading causes of death in our cohort. Hence, genetic testing may help reduce costs and fruitless investigations in affected infants. [ABSTRACT FROM AUTHOR]

Introduction: Urolithiasis is an increasingly common condition. Each patient after stone passage should have stone analysis performed. Every child with a urinary stone should be given a complete metabolic evaluation, and the stone analysis is an essential component of it. The aim of the study was to establish the relation between the metabolic profile of urolithiasis in children with idiopathic hypercalciuria and the composition of the excreted stone. Material and methods: The study included 26 children with urolithiasis (aged 1-17 years) from whom stones were obtained for the analysis. The urine pH and the 24-hour urine excretion of calcium, phosphorus, magnesium and oxalate as well as spot urinalysis including ratio of crystalloids to creatinine from the second voided urine sample of the day were assessed. Urinary stones were analyzed by infrared spectroscopy. The relation between the metabolic data and the stone type was then analyzed, taking into account two types of minerals: stones with a predominance of calcium oxalate dihydrate (weddellite) and calcium oxalate monohydrate (whewellite). Results: No correlation was found between the individual serum metabolic parameters of the patient and the composition of excreted stones. Substantially lower urinary excretion of phosphates, oxalate, magnesium and lower urinary pH were found in the group with predominant weddellite stones. A reduced value of each of these 4 variables increased more than sixfold the chance of diagnosing urolithiasis with stone composed of over 60% weddellite. Conclusions: The urinary metabolic profile is associated with the composition of renal stones estimated in infrared spectroscopy in children with idiopathic hypercalciuria. The coexistence of several urinary excretion anomalies improves the prediction of the composition of the stones. [ABSTRACT FROM AUTHOR]

The antioxidant activity capacities of some plants, and their inhibitory effects on the HMG-CoA reductase enzyme, the rate-determining enzyme of cholesterol synthesis, were investigated in our study. Antioxidant activity capacity and inhibitory effect of the HMG-CoA reductase enzyme were detected in all plant extracts used in our research. From the results obtained, it was determined that both antioxidant activity and % inhibition values of HMG-CoA reductase enzyme increased as the plant extracts concentration increased. The strongest ABTS and DPPH radical scavenging activities were exhibited by pomegranate fruit extract (IC50= 1.07 ±0.04 mg/mL and IC50= 0.39 ±0.01 mg/mL, respectively). At the same time, lemon had the strongest DMPD radical scavenging activity (IC50= 9×10-4 ±6×10-5 mg/mL). The best HMG-CoA reductase inhibitory activity was observed in persimmon fruit extract (IC50= 0.71 ±0.18 μg/mL). The inhibitory power of this extract was much higher than that of the enzyme’s standard inhibitor, Atorvastatin (IC50= 1.76 ±0.12 μg/mL). The extracts' potent antioxidant and inhibitory properties can be attributed to the rich phytochemical composition of plant extracts. Thus, it may be a potential source of new bioactive compounds effective against oxidative stress, hypercholesterolemia and cardiovascular complications. [ABSTRACT FROM AUTHOR]

Background: Amber necklaces have been used frequently to reduce the complaints of babies during teething. In this study, the knowledge and experience of families regarding the use of amber necklaces investigated. Methods: The structured questionnaire was applied face-to-face to parents with a 4–24 month old baby who applied to the paediatric outpatient clinic. Results: One hundred one families participating in the study reported that they used the amber necklace most frequently for restlessness (n = 72, 71.3%). Eighty- three% of families reported that the amber necklace was beneficial. It determined that 2% of the babies had suffocation and 2% had problems dispersing the grains. Conclusion: Although the parents think that the use of amber necklaces is effective during the teething period, they are not aware of the risks. It is important for healthcare professionals to inform their families about teething and especially the risks of using amber necklaces. [ABSTRACT FROM AUTHOR]

Background Serum calcium is at its lowest level within 24-48 hours after birth, rendering the neonate vulnerable to hypocalcemia. In our center, despite prophylactic administration of 200 mg/kg/day calcium gluconate, the prevalence of neonatal hypocalcemia remains high. Objective To determine the prophylactic efficacy of 400 vs. 200 mg/kg/day calcium gluconate in preventing neonatal hypocalcemia. Methods A randomized clinical trial with a pre- and post-test experimental design was done on neonates who fasted or received only minimal enteral feeding. Subjects were randomized to receive either 400 mg/kg/day (intervention group) or 200 mg/kg/day (control group) of intravenous calcium gluconate. We compared serum ionized calcium levels on the first day of admission before calcium gluconate administration and on the third day of hospitalization between the intervention and control groups. Results The median ionized calcium levels in the intervention vs. control group before calcium gluconate administration was 1.16 (range 0.4-2.4) mmol/L vs. 1.15 (range 0.6-4.5) mmol/L, respectively (P=0.561). After three days of calcium gluconate administration, the median ionized calcium level was 1.19 (range 0.7-1.45) mmol/L vs. 1.19 (range 0.68-4.6) mmol/L in the intervention vs. control group, respectively (P=0.828). The difference in pre- vs. post-administration ionized calcium levels was significant within the intervention group (P=0.032), but not within the control group (P=0.128). Conclusion Prophylactic intravenous calcium gluconate at 400 mg/kg/day was not more effective in preventing neonatal hypocalcemia than 200 mg/kg/day. [ABSTRACT FROM AUTHOR]

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Objective: Pathologic results in expanded metabolic screening tests may be due to the medications, inappropriate sampling methods, or the maternal originated inborn errors of metabolism. The aim of this study is to identify mothers with inborn errors of metabolism through the pathologic expanded metabolic screening results of their babies. Materials and Methods: Babies who were under 1 year of age and had a pathologic result of an expanded newborn screening for inborn errors of metabolism and their mothers were included in this retrospective single-centered study. Data of expanded metabolic screening results of both babies and their mothers were recorded. Clinical and laboratory findings relevant to suspected inborn errors of metabolism due to the pathologic screening results analysis were also noted for the mothers. Results: Seventeen babies and their mothers were enrolled. Expanded metabolic screening results were found compatible with inborn errors of metabolism in 4 (23.5%) of 17 mothers. Two of these mothers were diagnosed with 3-methylcrotonyl-CoA carboxylase deficiency and 2 mothers were diagnosed with glutaric aciduria type 1. Conclusion: Inborn errors of metabolism can present in any period of life, and this is the first study to address the importance of metabolic screening via tandem mass spectrometry in terms of early diagnosis of inborn errors of metabolism not only in pediatric aged patients but also in adulthood in Turkey. The performance of expanded metabolic screening tests may be an important step in terms of detecting maternal inborn errors of metabolism that are not diagnosed until adulthood. [ABSTRACT FROM AUTHOR]

Background: Delirium is an acute and transient disorder of brain function that often occurs in post‐surgical patients. Rivastigmine is a cholinesterase inhibitor drug that has been proposed as an adjuvant drug in recent years, still, despite significant theoretical evidence, few clinical studies have been performed on its impact on delirium. Aim: Due to the widespread use of cholinesterase inhibitors in pediatric and adult surgery, the present study aims to investigate the impact of Rivastigmine as a cholinesterase inhibitor on delirium after radical surgery. Methods: In this randomized double‐blind clinical trial, a hundred recruited patients were randomly assigned to either Rivastigmine (n = 50) or placebo (n = 50) groups, and we measured post‐operative impact on delirium, by Confusion Assessment Method (CAM) score, and cognitive impairment, by the Mini‐Mental State Examination (MMSE). Our univariate and multivariate logistical regression models assessed this hypothesized impact. Results: Treatment with Rivastigmine was significantly associated with reduced day one post‐op delirium, as measured by CAM score (Odds Ratio (OR) = 0.35, 95% Confidence Interval (CI) 0.11 to 0.97, p = 0.05), and cognitive impairment, as measured by MMSE (OR = 0.25, 95% CI 0.1 to 0.59, p = 0.0022). These associations became stronger after controlling for age, blood loss, and post‐op blood sodium levels: Delirium (OR = 0.23, 95% CI 0.05 to 0.92, p = 0.05), cognitive impairment (OR = 0.12, 95% CI 0.03 to 0.42, p = 0.000178). Conclusion: The significant result of our randomized clinical trial is that pre‐op Rivastigmine treatment may be associated with a substantial drop in patients experiencing post‐op delirium and post‐op cognitive impairment. Key points: Delirium is an acute and transient disorder of brain function that often occurs in post‐surgical patients.Rivastigmine is a cholinesterase inhibitor drug that has been proposed as an adjuvant drug in recent years, still, despite significant theoretical evidence, few clinical studies have been performed on its impact on delirium.In this randomized double‐blind clinical trial, a hundred recruited patients were randomly assigned to either Rivastigmine (n = 50) or placebo (n = 50) groups.The Confusion Assessment Method (CAM) was used to assess delirium as a binomial variable.Mini‐Mental State Examination (MMSE) instruments were also used to assess the patient's cognitive status, performed on the first day after surgery.Treatment with Rivastigmine was significantly associated with decreased day one post‐op delirium. [ABSTRACT FROM AUTHOR]

Plant-based diets may increase the risk of vitamin B12 deficiency due to limited intake of animal-source foods, while dietary folate increases when adhering to plant-based diets. In this cross-sectional study, we evaluated the B12 and folate status of Norwegian vegans and vegetarians using dietary B12 intake, B12 and folic acid supplement use, and biomarkers (serum B12 (B12), plasma total homocysteine (tHcy), plasma methylmalonic acid (MMA) and serum folate). Vegans (n 115) and vegetarians (n 90) completed a 24-h dietary recall and a FFQ and provided a non-fasting blood sample. cB12, a combined indicator for evaluation of B12 status, was calculated. B12 status was adequate in both vegans and vegetarians according to the cB12 indicator; however 4 % had elevated B12. Serum B12, tHcy, MMA concentrations and the cB12 indicator (overall median: 357 pmol/l, 9·0 µmol/l, 0·18 µmol/l, 1·30 (cB12)) did not differ between vegans and vegetarians, unlike for folate (vegans: 25·8 nmol/l, vegetarians: 21·6 nmol/l, P = 0·027). Serum B12 concentration < 221 pmol/l was found in 14 % of all participants. Vegetarians revealed the highest proportion of participants below the recommended daily intake of 2 µg/d including supplements (40 v. 18 %, P < 0·001). Predictors of higher serum B12 concentrations were average daily supplement use and older age. Folate deficiency (< 10 nmol/l) was uncommon overall (< 2·5 %). The combined indicator cB12 suggested that none of the participants was B12-depleted; however, low serum B12 concentration was found in 14 % of the participants. Folate concentrations were adequate, indicating adequate folate intake in Norwegian vegans and vegetarians. [ABSTRACT FROM AUTHOR]

Objective: Sialic acid, hexoses, hexosamines and fucose are components of glycoprotein, glycolipid and/or ganglioside. These glycoconjugates are essential components of cellular membrane and receptors, which are required for normal cellular activities. The levels of these aforementioned glycans are likely to be obstructed under biological conditions (such as oxidative stress) that leads to cellular and tissue damage. Despite the efficacy of valproate as a broad-spectrum antiepileptic drug, it administration is linked to oxidative stress and multiple organ damage. Moringa oleifera leaves have been proven to be bioactive food with diverse biochemical benefits, that include antioxidant, wound healing and tissue protective effects. Methods: In this study, female Sprague-Dawley rats were grouped into four. Group 1: control group given physiological saline; Group 2: animals given only 70% ethanol Moringa leaves extract (0.3 g/kg b.w./day); Group 3: animals that received only sodium valproate (0.5 g/kg b. w./day); Group 4: animals given similar dose of sodium valproate + Moringa extract. The treatments were administered orally for 15 days, and the animals were then fasted overnight and sacrificed. Stomach tissues collected were homogenized in ice-cold normal saline, using a glass homogenizer to make up 10% w/v tissue homogenate. Results: Analysis revealed that valproate administration resulted in elevated levels of sialic acid, hexoses, hexosamine, and fucose in the stomach tissue homogenates. Conversely, the administration of Moringa extract mitigated the adverse effect of valproate on glycan levels. Conclusion: Thus, Moringa leave extract can be a good candidate for attenuating valproate-induced toxicity on stomach tissue. [ABSTRACT FROM AUTHOR]