Class IIb Research Articles

PENGEMBANGAN MEDIA PEMBELAJARAN SCRAPBOOK UNTUK MENINGKATKAN KETERAMPILAN MEMBACA SISWA KELAS II SEKOLAH DASAR

This research aims to describe the development of scrapbook learning media to improve the reading skills of second grade elementary school students. The research was carried out using the ADDIE Research and Development model, with stages of analysis, design, development, implementation and evaluation. The sampling technique was purposive sampling with a total of 63 students. Data collection tools include observation, questionnaires, test questions, and documentation. The trial design uses one group pretest-posttest design. The test subjects were classes IIA, IIB and IIC at SDN 12 Jerora Sintang. The results of media development research and the results of students' reading skills are as follows. (1) The feasibility of the media by media experts was 97% and 93% by material experts was declared to be very feasible criteria and worthy of being tested on students. (2) The results of small group students' reading skills in the pretest class IIB were 23% while the posttest was 86% and in the large group trial in the pretest class IIA 32% while the posttest was 86%, then the pretest class IIC was 27% while the posttest was 82%, from the data the results were obtained. students' reading skills improved significantly. (3) The response of the small group of students in class IIB was 89%, while the large group in class IIA was 93% and in class IIC 92% was categorized as very good.

Thirty days clinical outcomes following stent implantation with aspirin-free prasugrel monotherapy in non-ST segment elevation myocardial infarction. Interim report from ASET-Japan pilot study

Abstract Background Dual antiplatelet therapy with a P2Y12 inhibitor, in addition to aspirin, is the standard therapy after percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) to prevent ischemic cardiovascular events. The Acetyl-Salicylic Elimination Trial (ASET) pilot studies conducted in Japan in patients with NSTE-ACS investigated the safety and feasibility of a low-dose prasugrel monotherapy after PCI. Purpose To ensure the safety of the patients, enrolment in the study was implemented only after confirmation of a successful procedure. The abstract reports our interim analysis, aimed at evaluating preliminary safety and feasibility. Methods The ASET-Japan pilot study was designed to explore the feasibility and safety of a low dose of prasugrel monotherapy (3.75mg/day), without adjunctive aspirin, after optimal PCI using Everolimus eluting stent (EES) in Japanese patients with non-ST-segment elevation acute coronary syndromes. The primary endpoint in the ASET-Japan NSTE-ACS (Phase 2) is a 12-month clinical outcome. The study is currently in the follow-up phase. All the target lesions were treated with a platinum-chromium everolimus-eluting stent. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis, and the primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding up to 12-month. If more than 3 events occurred, trial enrollment would have to be terminated by the data and safety monitoring board. Results One hundred one patients were enrolled after successful index PCI and completed a 30 days follow-up. The mean age was 69.1±12.3 years and 75.2% was male. The mean anatomical SYNTAX score was 7.9±4.7. Unstable angina (UAP) and NSTEMI were seen in 24.8% (25/101) and 75.2% (75/101) patients, respectively. According to the Braunwald classification, 8 percent of the patients were categorised as Class IA UAP, 48% as Class IB, 20% as Class IIB, 4% as Class IIIA and 20% as Class IIIB. In NSTEMI patients, the median (IQR) pre-procedural troponin value (cardiac Troponin T or I) was 2.79 (1.12 – 22.27) times the Upper Limit of Normal. According to the PRECISE DAPT score, 36.6% of patients were categorised as High Bleeding Risk (HBR) with scores above 25. At one month, the primary ischemic endpoints of cardiac death, target-vessel spontaneous MI or definite Stent thrombosis did not occur. Two patients (2.0%) had BARC type 3a bleeding. Conclusion Prasugrel monotherapy in the first 30 days following platinum-chromium everolimus-eluting stent deployment is a feasible and safe strategy in NSTE-ACS patients with simple anatomy and successful PCI.

Assessment of mechanical dyssynchrony can improve the new ESC-2021 guidelines for cardiac resynchronization therapy

Abstract Background In 2021, new guidelines for cardiac resynchronization therapy (CRT) were published by the European society of cardiology (ESC-2021), where the different classes of recommendations were based on a new ECG-based definition of left bundle branch block (LBBB). However, its association with reverse LV remodeling and additive prognostic value remain unknown. Aim To investigate (1) the association between the ESC-2021 CRT guidelines and reverse LV remodeling at follow up, and (2) the additive prognostic value of baseline assessment of mechanical dyssynchrony to the ESC-2021 guidelines. Methods We investigated 244 heart failure patients in sinus rhythm treated with CRT in two European centers. 70% of the population were males. Mean age was 69 ± 10 years, QRS duration: 154 ± 24 msec. Mechanical dyssynchrony at baseline was defined as the presence of apical rocking or septal flash (ApRock/SF) in 2D transthoracic echocardiography. LV volumes were measured at baseline and at 12 ± 6 months after CRT, where the amount of CRT induced reverse LV remodeling was calculated as the percent change of LVESV at follow-up compared to baseline. Results Applying the ESC-2021 LBBB definition, only 18% (n=45) of patients had LBBB. Applying the guidelines, only 14% (n=35) had class I recommendation (LBBB + QRS ≥ 150 msec), 44% (n=107) had class IIa (LBBB + QRS 130-149 msec or non-LBBB + QRS ≥ 150 msec), 29% (n=70) had class IIb (Non-LBBB + QRS 130-149 msec), and 13% (n = 33) were not recommended according to the ESC-2021 because of having baseline QRS duration between 120 and 129 msec. On the other hand, ApRock/SF was evident in 57% (n=140) of the patients. There was non-significant difference in the relative decrease in LVESV at follow up between patients with LBBB and non-LBBB applying the new LBBB definition (44% [IQR: 32-63], vs. 39%, IQR [20-57], P = 0.08, panel A). Similarly, there was no significant difference in the relative decrease in LVESV at CRT follow up among the four guideline recommendation classes, panel B. We combined presence of mechanical asynchrony at baseline with each of the guideline recommendation classes. The combination of ApRock/SF with classes IIa and IIb improved the prediction of reverse LV remodeling significantly (P<0.001 and <0.01 respectively), while adding mechanical asynchrony did not significantly improve prediction in the class I and the not-recommended subgroups. However, results of these last 2 may have been impacted by a small number of patients, panel C. Conclusion The new ESC-2021 definition of LBBB is associated with few patients with LBBB and consequently small number of patients with class I recommendation according to the new guidelines. There was weak association between the new ESC-2021 guideline classes of recommendation and reverse LV remodeling after CRT. However, baseline assessment of ApRock and SF can significantly improve the guidelines in predicting CRT outcome.

Hemodynamic effects of vericiguat in symptomaticHFrEF patients: insights from right heart catheterization study

Abstract Background Vericiguat is recommended in the guidelines as Class IIb for patients with heart failure with reduced ejection fraction (HFrEF) who continue to have persistent symptoms despite receiving standard therapy. However, the precise effects of vericiguat on pulmonary and systemic hemodynamics and cardiac performance remain unclear. Purpose This study aimed to investigate the hemodynamic impact of vericiguat in 12 symptomatic HFrEF patients who experienced worsening HF despite receiving standard therapy with the four foundational heart failure medications, using right heart catheterization (RHC). Methods On day 1, RHC was performed via the right internal jugular vein and a balloon-tripped pulmonary artery thermodilution catheter was placed. On day 2 and 3, RHC data were measured at 15min before and 30min, 1hr, 2hr, 3hr and 5hr after intake of 2.5mg vericiguat. RHC data on day 2 and 3 were averaged and the catheter was removed after the RHC measurements on day 3. RHC was repeated on a median day of 105(quartiles 37,168). The acute hemodynamic effects of vericiguat were assessed using a comparison of six RHC measures, including pulmonary artery wedge pressure (PAWP), mean pulmonary artery pressure (MPAP), mean arterial blood pressures (MABP), pulmonary (PVR) and systemic vascular resistances (SVR) and cardiac index (CI), at 15minutes before intake of vericiguat 2.5mg with those at 30minutes to 5hours after that. The chronic hemodynamic effects of vericiguat were evaluated by comparing the six RHC measures on day 1 with those on day 105(37,168). Results Participant characteristics on day 1 were age 63.5(53.5,70)yrs., 16.7%(N=2) women, height 164.3(155,171.3)cm, weight 64.6(54.8,75.1)kg, body mass index 23.8(20,26.3), systolic 101.5(90.5,111.5)mmHg and diastolic blood pressures 60.2(53.5,65)mmHg, heart rate 65.5(56,72)bpm, New York Heart Association functional class Ⅱ 50%(N=6), Ⅲ 16.7%(N=2) and Ⅳ 33.3%(N=4), estimated glomerular filtration rate 44.5(34.5,53.5)mL/min/1.73m2, left-ventricular ejection fraction 19.9(14.5,24.5)% and diastolic diameter 68(60.5,72.5)mm, left-atrial diameter 45(36.5,50.5)mm and brain natriuretic peptide level 419(254,479)pg/mL. Oral intake of vericiguat 2.5mg decreased PAWP (11[7.5,15]mmHg) and MPAP (19.3[14.3,26.8]mmHg) before the intake to PAWP (9.3[6.8,14]mmHg) and MPAP (17.5[12.5,24]mmHg) at 30min after that (both P<0.05[crude P<0.0017])(Figure A) while comparable changes in MABP, PVR, SVR and CI and the other timepoints (all P>0.05[crude P<0.0017]). Vericiguat was titrated to 2.5mg 25% (N=3), 5mg 50% (N=6) and 10mg 25% (N=3) on day 105 (37,168), in which PAWP (9.5[6.5,12.5]mmHg) was decreased from PAWP (14.5[9.5,19.5]mmHg) on day 1 (P<0.05[crude P<0.0083])(Figure B) while comparable changes in the other RHC parameters (all P>0.05[crude P<0.0083]). Conclusions The consistent reduction in PAWP underscores vericiguat's well-tolerated nature and potential to enhance cardiac performance in patients with HFrEF.

Reassessing pharmacological trials with positive composite outcome driven by reduction in nonfatal myocardial infarction: a systematic review and meta-analysis

Abstract Background Nonfatal myocardial infarction (MI) inadequately predicts cardiovascular and all-cause mortality in contemporary RCTs. The perceived efficacy of new treatments could be overstated if positivity in composite outcome is primarily attributed to reduction in nonfatal MI. Purpose This study seeks to assess pharmacological RCTs with positive results influenced by nonfatal MI reductions and scrutinize the associated clinical guideline recommendations. Methods Pharmacological RCTs focusing on mortality and nonfatal MI published from 2000 to 2023 were searched in PubMed and Web of Science, with subsequent citation tracking in Web of Science and Google Scholar for candidate RCTs referenced in English-language clinical guidelines. Main outcomes included: 1) relative risk reduction in the composite outcome excluding nonfatal MI; 2) relevant guideline recommendations based on the supporting trials. The impact of nonfatal MI on composite outcome was assessed by using the leave-one-out method. Meta-analysis utilized a random effects model. Results After reviewing 19,825 records, we identified 8 RCTs where positive composite outcomes were driven by reductions in non-fatal MI (Figure 1A). These were divided into three therapeutic groups: anti-thrombotic (3 trials), lipid-lowering (3 trials), and anti-inflammatory (2 trials). In guidelines citing these RCTs, lipid-lowering trials (IMPROVE-IT, FOURIER, CLEAR Outcomes; the latter has not been cited yet; a total of 60 recommendations across 17 guidelines; Figure 2) outperformed anti-thrombotic (27 recommendations across 15 guidelines) and anti-inflammatory trials (3 recommendations in 3 guidelines), with significantly higher Class I (45%) and IIa (33.3%) recommendations, and fewer Class IIb (21.7%) recommendations, compared to anti-thrombotic (0%, 22.2%, 66.7%) and anti-inflammatory (0%, 0%, 100%) trials (Figure 1B). In a meta-analysis of all trials on combined intensive lipid-lowering on top of maximally-tolerated statins (the ODYSSEY OUTCOMES, IMPROVE-IT, and FOURIER trials), the exclusion of nonfatal MI data sustained the negative findings (HR 0.94, 95% CI: 0.88 to 1.01). Conclusions Despite the overestimation of efficacy in certain anti-thrombotic, anti-inflammatory, and lipid-lowering RCTs due to the inclusion of nonfatal MI, lipid-lowering trials, particularly those supporting combined intensive therapy with statins, still receive disproportionately favorable guideline recommendations. This underscores the need to reassess the strength of evidence for these trials in guidelines, advocating for a more equitable and evidence-based approach to cardiovascular guideline recommendations.

Superficial circumflex iliac perforator flaps for maxilla defects with intraoral anastomosis or pedicle elongation techniques

BackgroundTo evaluate the feasibility and safety of the superficial circumflex iliac perforator flap (SCIP) for maxillary reconstruction with intraoral anastomosis, pedicle elongation, and super-microsurgery techniques to overcome its anatomical shortcomings due to the attractive merits of the flap.MethodsPatients who underwent reconstruction of maxillary defects with SCIPs from July 2020 to December 2022 were included. Intraoral anastomosis, pedicle elongation, and super-microsurgery were performed during surgery with or without a neck incision. The sizes, pedicle lengths, inner calibres of vessels, complications and flap survival statuses were recorded.ResultsA total of 12 patients were included, with 3 males and 9 females, and the median age was 45 years, ranging from 14 to 74 years. There were 5 class IIa and 7 class IIb defects, 6 cases underwent maxillary defect reconstruction via SCIPs with intraoral anastomosis, and the other 6 cases with distally design and/or de-epidermis pedicle elongation. Super-microsurgery interventions were needed in 5 patients. The size ranged from 3 cm×4 cm to 6 cm×8 cm. The pedicle length ranged from 4 cm to 12 cm, with a median of 6 cm. The inner caliber of the arteries ranged from 0.7 mm to 2 mm, with a median of 1 mm, and the veins ranged from 1.5 mm to 4 mm, with a median of 2.5 mm. All the flaps survived, and no donor site complications occurred.ConclusionSuperficial circumflex iliac perforator flaps can be regarded as feasible and safe choices for maxillary defects with the support of intraoral anastomosis, pedicle elongation and super-microsurgery.

Matings Between Individuals with Similar Major Histocompatibility Complex (MHC) Improve Offspring Survival in the Rainbow Trout (Oncorhynchus mykiss)

The major histocompatibility complex (MHC) consists of genes involved in immune response and molecular discrimination between self and non-self. MHC genes are the most polymorphic in vertebrates. The origin and maintenance of polymorphism in MHC genes in populations is still unresolved. Mechanisms such as sexual selection and heterozygote advantage have been suggested as explanations for this high variability. In this study, a farmed population of rainbow trout (Oncorhynchus mykiss) characterized by the presence of specific MHC class IIB gene haplotypes at a frequency higher (30%) than that expected from random matings was investigated. Therefore, it was hypothesized that disassortative matings occur with an adaptive advantage for females, resulting in improved reproductive performance when mated with individuals with similar MHC haplotypes. Genetic analyses of the breeders were performed to define the MHC haplotypes and to perform specific matings. The effect of mating was evaluated by analyzing the survival rate of the offspring at various stages of incubation until swim-up. The reproductive performance of the offspring derived from specimens with similar haplotypes showed a better survival trend during the first life stages and reduced malformations. The results obtained are in contrast with the heterozygous advantage theory, therefore it was hypothesized, as for other salmonid species, the presence of a positive selection towards locally adapted MHC genes that promotes reproduction between genetically similar individuals.

Program Deteksi Dini Skrining Kesehatan Mental Bagi Warga Binaan Di Rumah Tahanan Kelas IIB Kebumen

Introduction: Background According to American psychotic association, Mental health is the result of a successful adjustment or lack of psychopathology. It also refers to a state in which one does not experience a breakdown in psychological aspects, emotional, eehavior, and social. According to who's regional asia Pacific in Indonesia, There are 9,162.886 cases or 3.7 %s of the population. According to basic health research 2018, the case of mental or mental illness in Indonesia has improved, especially on the Central Java, where prevalence of mental illness is approximately 4.4 %. In the prison house, An inmate will face various problems and sufferings. Theoretically, The major suffering the inmates suffered was the loss of freedom of movement. However, There's extra suffering from the loss of this freedom, which is: 1). Lost the chance to have sexual relations. 2). Loss of privacy rights. 3). Lost access to getting help and kindness. 4). Lost personal secrecy due to a negative stigma of society.5). Feeling the infantile process, it's the treatment that makes an adult feel like a child. Observe The purpose of this activity is to Detect Mental Health of Inmates in Kebumen Class IIB Prison. Method: This method of activity uses descriptive analysis methods Result and conclusion: According to the mental health screening prognosis that has been carried out to 135 inmates, the result of questionnaire depressive questionnaires 4.44 % is very bad, anxiety category 4.44 % is severe, and the stress category of 2.22 %s is very severe.Generated questionnaire 24,44 % has a GME/Psychotic /PTSD problem.

THE RELATIONSHIP BETWEEN SELF-ESTEEM AND RESILIENCE IN PRISONERS IN CORRECTIONAL INSTITUTIONS FEMALE CLASS II B PADANG

Correctional institutions are institutions used to train and guide law violators. Inmates during their prison period experience problems such as inner conflict, trauma, difficulty adapting, unstable emotions and anxiety. To be able to survive and adapt during the prison period inmates need the ability to adapt and overcome various problems that arise which are made with resilience, one of the factors that affect a person's resilience is self-esteem. Therefore, this study aims to see the relationship between self-esteem and resilience in female inmates of class IIB Padang. This study uses a quantitative research method with a correlational approach. The number of samples in this study was 53 inmates who were selected using purposive sampling techniques. Data collection was carried out using the resilience scale and self-esteem scale from Karimah (2022). The data analysis in this study uses product moment correlation analysis with the help of SPSS.26. The results of this study show that self-esteem has a relationship with resilience in inmates in class IIB Padang women's correctional institution.

Using the refined Developability Classification System (rDCS) to guide the design of oral formulations

The refined Developability Classification System (rDCS) provides a comprehensive animal-free approach for assessing biopharmaceutical risks associated with developing oral formulations. This work demonstrates practical application of a recently advanced rDCS framework guiding formulation design for six diverse active pharmaceutical ingredients (APIs) and compares rDCS classifications with those of the Biopharmaceutics Classification System (BCS). While the BCS assigns five of the APIs to class II/IV, indicating potentially unfavorable biopharmaceutical attributes, the rDCS provides a more nuanced risk assessment. Both BCS and rDCS assign acetaminophen to class I at therapeutic doses. Voriconazole and lemborexant (both BCS II) are classified in rDCS class I at therapeutic doses, indicating suitability for development as conventional oral formulations. Fedratinib is classified as BCS IV but the rDCS indicates a stratified risk (class I, IIa or IIb), depending on the relevance of supersaturation/precipitation in vivo. Voxelotor and istradefylline (both BCS II) belong to rDCS class IIb, requiring solubility enhancement to achieve adequate oral bioavailability. Comparing the rDCS analysis with literature on development and pharmacokinetics demonstrates that the rDCS reliably supports oral formulation design over a wide range of API characteristics, thus providing a strong foundation for guiding development.

PENGARUH METODE PEMBELAJARAN GQGA TERHADAP HASIL BELAJAR MATEMATIKA MATERI PEMBAGIAN UNTUK SISWA KELAS II SDN NGADI

This study aims to determine the effect of the Giving Question and Getting Answer (GQGA) learning method on the Mathematics learning outcomes of class II students at SD Negeri Ngadi. The study was conducted through the experimental method of pretest-posttest Control Group design. The subjects of this study were 30 students, with class IIA as the experimental class totaling 15 students and class IIB as the control class also totaling 15 students. The data collection tool used was a learning outcome test on division material. The data analysis technique used statistical analysis pair sample T-test. The results of the study showed a significant value of 0.00 <0.05. So H0 is rejected and Ha is accepted, it can be concluded that there is an effect of learning outcomes in the experimental group on the ability to achieve Mathematics learning outcomes on division material among class II students who use the GQGA learning method.

Effect of low-intensity aerobic cycling ergometer on ability to perform activity of daily living of patients with myasthenia gravis in RSUD Dr. Soetomo Surabaya

Background and objectives. Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction causing fluctuating skeletal muscle weakness and fatigue that result in increased restrictions on physical activity, affecting the patient's ability to perform daily activities in the family, social, and work environment. The MG-ADL scale is an assessment of the ability of the daily activities of MG patients that does not require equipment or special skills for the examiner and can be done in a short time. This study analyzes the effect of low intensity aerobic exercise cycle ergometer on the ability to perform daily activities of MG patients. Materials and methods. Twenty-two MG patients, MGFA class IIa and IIb, aged 18–59, participated in this study. The subjects were randomly divided into a treatment group and a control group. The treatment group received aerobic cycle ergometer exercise for 30 minutes, three times per week, for eight weeks. Both groups were educated to continue medication from neurology, perform physical activity as usual, and breathing exercises. Assessment of MG-ADL performed before and after intervention. Results. There was an improvement in scores on breathing and lower limb function in the treatment group. There was significant decrease in MG-ADL scores at the intervention group (p = 0.000) with large effect size (1.09). The comparison of MG-ADL scores between groups showed a significant value (p = 0.009) with a large effect size (1.24). Conclusion. Low intensity aerobic exercise cycle ergometer for 8 weeks improves the ability to perform ADL in MG patient.

Differential Effects of HDAC6 Inhibition Versus Knockout During Hepatic Ischemia-Reperfusion Injury Highlight Importance of HDAC6 C-terminal Zinc-finger Ubiquitin-binding Domain.

Ischemia-reperfusion injury (IRI) causes significant morbidity in liver transplantation among other medical conditions. IRI following liver transplantation contributes to poor outcomes and early graft loss. Histone/protein deacetylases (HDACs) regulate diverse cellular processes, play a role in mediating tissue responses to IRI, and may represent a novel therapeutic target in preventing IRI in liver transplantation. Using a previously described standardized model of murine liver warm IRI, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were assessed at 24 and 48 h after reperfusion to determine the effect of different HDAC inhibitors. Broad HDAC inhibition with trichostatin-A (TSA) was protective against hepatocellular damage ( P < 0.01 for AST and P < 0.05 for ALT). Although HDAC class I inhibition with MS-275 provided statistically insignificant benefit, tubastatin-A (TubA), an HDAC6 inhibitor with additional activity against HDAC10, provided significant protection against liver IRI ( P < 0.01 for AST and P < 0.001 for ALT). Surprisingly genetic deletion of HDAC6 or -10 did not replicate the protective effects of HDAC6 inhibition with TubA, whereas treatment with an HDAC6 BUZ-domain inhibitor, LakZnFD, eliminated the protective effect of TubA treatment in liver ischemia ( P < 0.01 for AST and P < 0.01 for ALT). Our findings suggest TubA, a class IIb HDAC inhibitor, can mitigate hepatic IRI in a manner distinct from previously described class I HDAC inhibition and requires the HDAC6 BUZ-domain activity. Our data corroborate previous findings that HDAC targets for therapeutic intervention of IRI may be tissue-specific, and identify HDAC6 inhibition as a possible target in the treatment of liver IRI.

Synthesis and biological evaluation of ortho-phenyl phenylhydroxamic acids containing phenothiazine with improved selectivity for class IIa histone deacetylases

Class IIa histone deacetylases (HDACs) have been linked to tumorigenesis in various cancers. Previously, we designed phenylhydroxamic acid LH4f as a potent class IIa HDAC inhibitor. However, it also unselectively inhibited class I and class IIb HDACs. To enhance the compound’s selectivity towards class IIa HDACs, the ortho-phenyl group from the selective HDAC7 inhibitor 1 is incorporated into ortho position of the phenylhydroxamic acid in LH4f. Compared to LH4f, most resulting compounds displayed substantially improved selectivity towards the class IIa HDACs. Notably, compound 7 g exhibited the strongest HDAC9 inhibition with an IC50 value of 40 nM. Molecular modelling further identified the key interactions of compound 7 g bound to HDAC9. Compound 7 g significantly inhibited several human cancer cells, induced apoptosis, modulated caspase-related proteins as well as p38, and caused DNA damage. These findings suggest the potential of class IIa HDAC inhibitors as lead compounds for the development of cancer therapeutics.

Retention of implant retained obturator using two implant placement configurations for maxillectomy cases: in-vitro study

BackgroundImplant-retained obturators for maxillectomy cases have several advantages over traditional obturators but prosthetic design for specific conditions after maxillary resection has several challenges and the appropriate implant placement configuration is essential for improving retention and the stability of the implant-retained obturator.ObjectivesThe present study aimed to assess the retention force of using linear and nonlinear implant placement configurations using ball and socket attachment in implant-retained obturators at the initial retention and after simulation of six months of use.Materials and methodsTwo identical epoxy resin maxillary models of a completely edentulous unilateral maxillary defect (Brown’s class IIb) were used for implant placement, in the first model three implants were arranged with linear placement configuration, and in the second model three implants were arranged in nonlinear placement configuration. For proper sample sizing, 26 models and obturator were used. Two equal groups of obturators (13 for each group) were constructed, each with a different implant placement configuration. Both groups used the same attachment design (a non-splinted ball attachment). Using a cyclic loading machine that served as a dental insertion and removal simulator, each study group was subjected to 500 tension-compression cycles simulating 6 months of use. Using the universal testing machine, each obturator was removed at a speed of 50 mm/min for the crosshead. peak load to dislodgement was measured at the initial retention and after the simulations of six months of use. Data were analyzed using independent and paired t-tests while percent change was analyzed using the Mann Whitney U test.ResultsThere were a statistically significant differences in retention between the nonlinear implant placement configuration for Brown’s class IIb maxillectomy and the linear implant placement configuration at initial retention evaluation with p-value of < 0.0001 and after simulation of six months of usage with p-value of < 0.0001 Also, after simulation of 6 months of use group I lose − 24.87 (10.16) % of its retention while group II lose − 17.49 (7.78) %.ConclusionsNon-linear implant placement is more retentive at the initial retention and after simulation of six months of use than linear and loses less retention after usage.

Design, Synthesis, and Structural Evaluation of Acetylated Phenylthioketone Inhibitors of HDAC10.

Histone deacetylase 10 (HDAC10) is unique among the greater HDAC family due to its unusually narrow substrate specificity as a polyamine deacetylase, specifically as an N 8-acetylspermidine hydrolase. Polyamines are essential for cell growth and proliferation; consequently, inhibition of polyamine deacetylation represents a possible strategy for cancer chemotherapy. In this work, we have designed six acetylated phenylthioketone inhibitors of HDAC10 containing positively charged para- and meta-substituted amino groups designed to target interactions with E274, the gatekeeper that recognizes the positively charged ammonium group of the substrate N 8-acetylspermidine. We prepared each of these inhibitors through a short synthetic route of six steps. By adapting a low-cost colorimetric activity assay, we measured low-micromolar IC50 values for these compounds against a humanized construct of zebrafish HDAC10 (A24E-D94A HDAC10). Selected inhibitors were cocrystallized with A24E-D94A zebrafish HDAC10 and zebrafish HDAC6 to provide insight into class IIb isozyme affinity and selectivity.

Enhanced Recovery After Surgery (ERAS) cardiac turnkey order set for perioperative pain management in cardiac surgery: Proceedings from the American Association for Thoracic Surgery (AATS) ERAS Conclave 2023

ObjectiveOptimal perioperative pain management is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Several guidelines and expert consensus documents have been published to provide guidance on pain management and opioid reduction in cardiac surgery. Our objective is to consolidate that guidance into an evidence-based order set that will assist in the implementation of a comprehensive multimodal approach to pain management. MethodsSubject matter experts were consulted to translate existing guidelines and peer-reviewed literature into a sample turnkey order set for pain management. Orders derived from consistent Class I, IIA, or equivalent recommendations across referenced guidelines and consensus manuscripts appear in the order set in bold type. Selected orders that were inconsistently Class I or IIA, Class IIB, or supported by published evidence, were also included in italicized type. ResultsOpioid-based analgesia is associated with delayed recovery and opioid-related adverse events. Several multimodal medications have been shown to reduce reliance upon opioids. These include the scheduled use of acetaminophen, gabapentinoids, and nonsteroidal anti-inflammatory drugs. In addition, intravenous analgesics such as dexmedetomidine, ketamine, magnesium, and lidocaine have been shown to both complement the maintenance of anesthesia as well as optimize pain control postoperatively. Long-acting opioids remain a key component of pain management when provided to reduce the overall use of short-acting synthetic opioids or in direct response to break though pain after exhausting other alternatives. When applied in a bundled fashion, several studies have demonstrated a reduction in overall opioid administration and improved rates of postoperative recovery. ConclusionsThere has been increased awareness regarding the potential short- and long-term adverse effects of both inadequate analgesia and excessive opioid administration after cardiac surgery. This turnkey order set aims to facilitate implementation of a comprehensive approach toward provision of multimodal, opioid-sparing medications to optimize pain management in cardiac surgery.

HDAC6 Deletion Decreases Pristane-induced Inflammation.

Systemic lupus erythematosus is an autoimmune disease characterized by excessive inflammation and production of pathogenic Abs. Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase. It has been reported that selective HDAC6 inhibition decreases inflammation in lupus mouse models. In this study, sex- and age-matched wild-type (WT) and HDAC6-/- mice on the C57BL/6 background were administered 0.5 ml of pristane or PBS i.p. at 8-12 wk of age and were euthanized 10 d later. At sacrifice, body weight and spleen weight were measured, sera were collected, and splenocytes and peritoneal cells were harvested for flow cytometry. We found pristane administration increased the spleen weight with no difference between WT and HDAC6-/- mice. Pristane administration promoted the population of CD11b+Ly6C++ inflammatory monocytes and CD11b+Ly6G+ neutrophils. Peritoneal recruitment of these inflammatory monocytes and neutrophils was significantly decreased in HDAC6-/- mice compared with the WT mice. Flow cytometry results showed that the number of CD69+ T and B cells was increased in HDAC6-/- mice. Pristane administration also induced the IFN signature genes as determined by RT-qPCR. Furthermore, IFN signature genes were not affected in HDAC6-/- mice compared with the WT mice. In vitro studies in J774A.1 cells revealed that the selective HDAC6 inhibitor (ACY-738) increased acetylation of NF-κB while increasing Stat1 phosphorylation, which resulted in inducible NO synthase production in LPS/IFN-γ-stimulated cells. Taken together, these results demonstrate that although HDAC6 inhibition may inhibit some inflammatory pathways, others remain unaffected.

Genome-Wide Survey of the Potential Function of CrLBDs in Catharanthus roseus MIA Biosynthesis.

Catharanthus roseus (C. roseus) can produce over 150 types of monoterpenoid indole alkaloids (MIAs), including vinblastine and vincristine, which are currently the primary sources of these alkaloids. Exploring the complex regulatory mechanisms of C. roseus is significant for resolving MIA biosynthesis. The Lateral Organ Boundaries Domain (LBD) is a plant-specific transcription factor family that plays crucial roles in the physiological processes of plant growth, stress tolerance, and specialized metabolism. However, the LBD gene family has not been extensively characterized in C. roseus, and whether its members are involved in MIA biosynthesis is still being determined. A total of 34 C. roseus LBD (CrLBD) genes were identified. RNA-Seq data were investigated to examine the expression patterns of CrLBD genes in various tissues and methyl jasmonate (MeJA) treatments. The results revealed that the Class Ia member CrLBD4 is positively correlated with iridoid biosynthetic genes (p < 0.05, r ≥ 0.8); the Class IIb member CrLBD11 is negatively correlated with iridoid biosynthetic genes (p < 0.05, r ≤ -0.8). Further validation in leaves at different growth stages of C. roseus showed that CrLBD4 and CrLBD11 exhibited different potential expression trends with iridoid biosynthetic genes and the accumulation of vindoline and catharanthine. Yeast one-hybrid (Y1H) and subcellular localization assays demonstrated that CrLBD4 and CrLBD11 could bind to the "aattatTCCGGccgc" cis-element and localize to the nucleus. These findings suggest that CrLBD4 and CrLBD11 may be potential candidates for regulating MIA biosynthesis in C. roseus. In this study, we systematically analyzed the CrLBD gene family and provided insights into the roles of certain CrLBDs in the MIA biosynthesis of C. roseus.

Expanding the toolbox: Novel class IIb microcins show activity against Gram-negative ESKAPE and plant pathogens.

Interspecies interactions involving direct competition via bacteriocin production play a vital role in shaping ecological dynamics within microbial ecosystems. For instance, the ribosomally-produced siderophore bacteriocins, known as class IIb microcins, affect the colonization of host-associated pathogenic Enterobacteriaceae species. Notably, to date, only five of these antimicrobials have been identified, all derived from specific Escherichia coli and Klebsiella pneumoniae strains. We hypothesized that class IIb microcin production extends beyond these specific compounds and organisms. With a customized informatics-driven approach, screening bacterial genomes in public databases with BLAST and manual curation, we have discovered twelve previously unknown class IIb microcins in seven additional Enterobacteriaceae species, encompassing phytopathogens and environmental isolates. We introduce three novel clades of microcins (MccW, MccX, and MccZ), while also identifying eight new variants of the five known class IIb microcins. To validate their antimicrobial potential, we heterologously expressed these microcins in E. coli and demonstrated efficacy against a variety of bacterial isolates, including plant pathogens from the genera Brenneria, Gibbsiella, and Rahnella . Two newly discovered microcins exhibit activity against Gram-negative ESKAPE pathogens, i.e. Acinetobacter baumannii or Pseudomonas aeruginosa , providing the first evidence that class IIb microcins can target bacteria outside of the Enterobacteriaceae family. This study underscores that class IIb microcin genes are more prevalent in the microbial world than previously recognized and that synthetic hybrid microcins can be a viable tool to target clinically relevant drug-resistant pathogens. Our findings hold significant promise for the development of innovative engineered live biotherapeutic products tailored to combat these resilient bacteria.