Tandem Mass Tag LC-MS/MS of Aqueous Humor From Individuals With Type 2 Diabetes Without Retinopathy Reveals Early Dysregulation of Synaptic Proteins.

Purpose: An early neurodegenerative component of diabetic retinal disease (DRD) that precedes the vascular findings of clinically diagnosed diabetic retinopathy (DR) is increasingly being recognized. However, the relevant molecular mechanisms and biomarkers for early DRD are poorly defined. The purpose of this study was to uncover novel potential mediators of early diabetic retinal neuronal dysfunction through analysis of the aqueous fluid proteome in preclinical DR. Methods: Aqueous fluid was collected from subjects with type 2 diabetes mellitus (DM) but no clinical DR and from nondiabetic controls undergoing routine cataract surgery. Preoperative spectral-domain optical coherence tomography of the macula was obtained. Tandem mass tag LC-MS/MS was performed to identify proteins differentially present in diabetic and control aqueous fluid, and proteins with >50% change and P < 0.05 were considered significant. Selected results were validated with western blot of human aqueous fluid samples. Results: We identified decreased levels of proteins implicated in neuronal synapse formation and increased levels of inflammatory proteins in the aqueous fluid from patients with type 2 DM but no DR compared with controls. Of the differentially present synaptic proteins that we identified and confirmed with western blot, the majority have not previously been linked with DRD. Conclusions: The proteomic profile of aqueous fluid from individuals with type 2 DM but no DR suggests that retinal neuronal dysfunction and inflammation represent very early events in the pathophysiology of DRD. These findings support the concept that diabetic retinal neurodegeneration precedes vascular pathology and reveal novel potential mediators and/or biomarkers warranting further investigation.

Comparative Study on the Immunogenicity of COVID-19 mRNA Vaccines in Patients Receiving Adjuvant and Palliative Chemotherapy.

This study was conducted to investigate potential differences in vaccine efficacy between patients undergoing palliative chemotherapy and receiving adjuvant chemotherapy. Additionally, the study proved the influence of vaccination timing on vaccine efficacy during active chemotherapy. Anti-receptor-binding domain (RBD) IgG binding antibody assays and surrogate neutralizing antibody assays were performed after BNT162b2 or mRNA-1273 vaccination in 45 solid cancer patients (23 adjuvant and 22 palliative chemotherapy) and in 24 healthy controls before vaccination (baseline), at every two to four weeks after the first (post-dose 1) and the second vaccination (post-dose 2). The levels of anti-RBD IgG and neutralizing antibodies increased significantly from baseline through post-dose 1 to post-dose 2 in all three groups. At the post-dose 1, the anti-RBD IgG and neutralizing antibody levels were significantly lower in cancer patients than in healthy controls. However, by post-dose 2, the seropositivity of anti-RBD IgG and neutralizing antibodies uniformly reached 100% across all groups, with no significant disparity in antibody levels among the three groups. Moreover, the antibody titers were not significantly different between patients with a vaccine and chemotherapy interval of more than 14 days or those with less than 14 days. This study demonstrated that after second doses of mRNA COVID-19 vaccines, humoral immune responses in patients receiving chemotherapy were comparable to those of healthy controls, regardless of whether the purpose of the anti-cancer treatment was palliative or adjuvant. Furthermore, the timing of vaccination did not affect the level of humoral immunity after the second vaccination.

Comprehensive evaluation of nutritional components, bioactive metabolites, and antioxidant activities in diverse sorghum (Sorghum bicolor (L.) Moench) landraces.

Sorghum, one of the prospective crops for addressing future food and nutrition security, has received attention in recent years due to its health-promoting compounds. It is known that several environmental and genetic factors affect the metabolite contents of dietary crops. This study investigated the diversity of different nutrients, functional metabolites, and antioxidant activity using three different assays in 53 sorghum landraces from Korea, China, Japan, Ethiopia, and South Africa. The effects of origin and seed color variations were also investigated. Total phenolic (TPC), total tannin (TTC), total fat, total protein, total dietary fiber, and total crude fiber contents all varied significantly among the sorghum landraces (p < 0.05). Using a gas chromatography-flame ionization detector, palmitic, stearic, oleic, linoleic, and linolenic acids were detected in all the sorghum landraces, and their content significantly varied (p < 0.05). Furthermore, four 3-deoxyanthocyanidins (luteolinidin, apigeninidin, 5-methoxyluteolinidin, and 7-methoxyapigeninidin) and two flavonoids (luteolin and apigenin) were detected in most of the landraces using liquid chromatography-tandem mass spectrometry, and their concentrations also significantly varied. Statistical analyses supported by multivariate tools demonstrated that seed color variation had a significant effect on TPC, TTC, DPPH• and ABTS•+ scavenging activities, and ferric-reducing antioxidant power, with yellow landraces having the highest and white landraces having the lowest values. Seed color variation also had a significant effect on dietary fiber, linoleic acid, linolenic acid, and luteolin contents. In contrast, all nutritional components and fatty acids except total protein and oleic acid were significantly affected by origin, while most 3-deoxyanthocyanidins and flavonoids were unaffected by both origin and seed color differences. This is the first study to report the effect of origin on sorghum seed metabolites and antioxidant activities, laying the groundwork for future studies. Moreover, this study identified superior landraces that could be good sources of health-promoting metabolites.

Exploring the potentials of sorghum genotypes: a comprehensive study on nutritional qualities, functional metabolites, and antioxidant capacities.

Introduction: Sorghum, long regarded as one of the most underutilized crops, has received attention in recent years. As a result, conducting multidisciplinary studies on the potential and health benefits of sorghum resources is vital if they are to be fully exploited. In this study, the nutritional contents, functional metabolites, and antioxidant capacities of 23 sorghum breeding lines and three popular cultivars were assessed. Materials and method: All of the sorghum genotypes were grown under the same conditions, and mature seeds were hand-harvested. The metabolite contents and antioxidant capacities of sorghum seeds were assessed using standard protocols. Fatty acids were quantified using a gas chromatography-flame ionization detector, whereas flavonoids and 3-deoxyanthocyanidins were analyzed using a liquid chromatography-tandem mass spectrometry method. The data were analyzed using both univariate and multivariate statistical approaches. Results and discussion: Total protein (9.05-14.61%), total fat (2.99-6.91%), crude fiber (0.71-2.62%), dietary fiber (6.72-16.27%), total phenolic (0.92-10.38 mg GAE/g), and total tannin (0.68-434.22 mg CE/g) contents varied significantly across the sorghum genotypes (p < 0.05). Antioxidant capacity, measured using three assays, also differed significantly. Five fatty acids, including palmitic, stearic, oleic, linoleic, and linolenic acids, were found in all the sorghum genotypes with statistically different contents (p < 0.05). Furthermore, the majority of the sorghum genotypes contained four 3-deoxyanthocyanidins, including luteolinidin, apigeninidin, 5-methoxyluteolinidin, and 7-methoxyapigeninidin, as well as two dominant flavonoids, luteolin and apigenin. Compared to the cultivars, some breeding lines had significantly high levels of metabolites and antioxidant activities. On the other hand, statistical analysis showed that total tannin, total phenolic, and antioxidant capacities varied significantly across white, yellow, and orange genotypes. Principal component analysis was used to differentiate the sorghum genotypes based on seed color and antioxidant index levels. Pearson's correlation analysis revealed strong links between biosynthetically related metabolites and those with synergistic antioxidant properties. Conclusion: This research demonstrated the diversity of the sorghum resources investigated. Those genotypes with high levels of nutritional components, functional metabolites, and antioxidant activities could be used for consumption and breeding programs.

Positivity rates of mycobacterial culture in patients with tuberculous spondylitis according to methods and sites of biopsies: An analysis of 206 cases.

OBJECTIVES: We aimed to evaluate the mycobacterial culture positivity rates according to biopsy methods and sites in patients with tuberculous spondylitis (TS) and identify which tissues are the best sites for the diagnosis of TS. METHODS: We retrospectively identified and reviewed medical records of all patients with TS in three university-affiliated hospitals in the Republic of Korea from January 2003 to December 2020. TS was diagnosed by culture or histopathologic examination of vertebral bodies or paraspinal tissues and characteristic clinical and radiologic features. Patients with TS who received a needle biopsy or underwent surgical biopsy were investigated. The sites of needle biopsy were classified as vertebral bodies or paraspinal tissues. RESULTS: During the study period, 206 tissues from 200 patients with TS were included in the analysis. The culture positivity rates of vertebral bodies obtained by needle biopsy, paraspinal tissues obtained by needle biopsy, and tissues obtained by surgery were 69.0%, 85.3%, and 83.2%, respectively. Multivariate logistic regression identified that paraspinal tissues as biopsy sites were independently associated with mycobacterial culture positivity in TS undergoing needle biopsy (adjusted odds ratio, 3.68; 95% confidence interval: 1.13-11.99, P = 0.030). CONCLUSIONS: We demonstrated that the positivity rates of mycobacterial culture in TS were 69.0-85.3%. Paraspinal tissues as biopsy sites were significantly associated with culture positivity in needle biopsy, suggesting that targeting paraspinal tissues during needle biopsy may be the best method for diagnosing TS.

Optimized 3D Bioprinting Technology Based on Machine Learning: A Review of Recent Trends and Advances.

The need for organ transplants has risen, but the number of available organ donations for transplants has stagnated worldwide. Regenerative medicine has been developed to make natural organs or tissue-like structures with biocompatible materials and solve the donor shortage problem. Using biomaterials and embedded cells, a bioprinter enables the fabrication of complex and functional three-dimensional (3D) structures of the organs or tissues for regenerative medicine. Moreover, conventional surgical 3D models are made of rigid plastic or rubbers, preventing surgeons from interacting with real organ or tissue-like models. Thus, finding suitable biomaterials and printing methods will accelerate the printing of sophisticated organ structures and the development of realistic models to refine surgical techniques and tools before the surgery. In addition, printing parameters (e.g., printing speed, dispensing pressure, and nozzle diameter) considered in the bioprinting process should be optimized. Therefore, machine learning (ML) technology can be a powerful tool to optimize the numerous bioprinting parameters. Overall, this review paper is focused on various ideas on the ML applications of 3D printing and bioprinting to optimize parameters and procedures.

Origin and seed coat color differently affect the concentrations of metabolites and antioxidant activities in soybean (Glycine max (L.) Merrill) seeds.

In this study, 54 soybean germplasms of different seed coat colors originated from America, China, Japan, and Korea were cultivated in Korea and analyzed for the contents of total oil, total protein, total phenolic, five fatty acids, and five isoflavones, and antioxidant activities using three assays. The soybeans showed significant variations (p < 0.05) of metabolite contents and antioxidant activities. Origin and seed coat color exhibited a slight or insignificant effect on total protein and total oil contents. In contrast, origin and seed coat color significantly affected the concentration of individual and total isoflavones, and total phenolics, with few exceptions. Whereas fatty acids were significantly affected by origin, seed coat color provided better information regarding the variations in antioxidant capacities. Together, multivariate and correlation analyses revealed important associations between biosynthetically-related metabolites. In general, origin and seed coat color differently influenced the concentration of different classes of metabolites and antioxidant activities.

Phylogeography and Antioxidant Activity of Proso Millet (Panicum miliaceum L.).

Proso millet (Panicum miliaceum L.) or broomcorn millet is among the most important food crops to be domesticated by humans; it is widely distributed in America, Europe, and Asia. In this study, we genotyped 578 accessions of P. miliaceum using 37 single-sequence repeat (SSR) markers, to study the genetic diversity and population structure of each accession. We also investigated total phenolic content (TPC) and superoxide dismutase (SOD) activity and performed association analysis using SSR markers. The results showed that genetic diversity and genetic distance were related to geographic location and the fixation index (Fst). Population structure analysis divided the population into three subpopulations. Based on 3 subpopulations, the population is divided into six clusters in consideration of geographical distribution characteristics and agronomic traits. Based on the genetic diversity, population structure, pairwise Fst, and gene flow analyses, we described the topological structure of the six proso millet subpopulations, and the geographic distribution and migration of each cluster. Comparison of the published cluster (cluster 1) with unique germplasms in Japan and South Korea suggested Turkey as a possible secondary center of origin and domestication (cluster 3) for the cluster. We also discovered a cluster domesticated in Nepal (cluster 6) that is adapted to high-latitude and high-altitude cultivation conditions. Differences in phenotypic characteristics, such as TPC, were observed between the clusters. The association analysis showed that TPC was associated with SSR-31, which explained 7.1% of the total variance, respectively. The development of markers associated with TPC and SOD will provide breeders with new tools to improve the quality of proso millet through marker-assisted selection.

Factors Affecting Cancer Prevention Behaviors and Cancer Screening in First-Degree Relatives of Breast and Colorectal Cancer Patients in Korea: A Cross-Sectional Study.

BACKGROUND: First-degree relatives (FDRs) of cancer patients have a high risk of cancer due to a similar lifestyle and genetic predisposition. However, previous studies rarely examined the level of cancer prevention behaviors and screening and affecting factors in cancer patients' FDRs. PURPOSE: This study aimed to describe the levels of cancer knowledge, attitudes toward cancer, cancer worry, perceived cancer risk, and cancer prevention behaviors and cancer screening in FDRs of breast and colorectal cancer patients. Moreover, it sought to identify factors affecting cancer prevention behavior and cancer screening. METHODS: A cross-sectional, descriptive correlational design was used. The study enrolled 138 FDRs of breast and colorectal cancer patients. Participants completed self-administered questionnaires at a tertiary hospital in Seoul, Korea. Descriptive statistics, frequencies, chi-square test, independent t test, one-way analysis of variance (ANOVA), Pearson's correlation, multiple regression, and logistic regression were performed for data analysis. RESULTS: The levels of perceived cancer risk, cancer knowledge, attitude toward cancer, and cancer prevention behaviors were moderate, while the level of cancer worry was high. Ninety-two participants reported having undergone cancer screenings, but the types of screening were not associated with their family history. Age, gender, and attitude toward cancer affected cancer prevention behaviors. The cancer screening rate was higher in older participants, in women, and in patients' FDRs with a longer cancer diagnosis. IMPLICATIONS FOR PRACTICE: Attitude was the modifiable factor for cancer prevention behaviors. Nurse-led educational and counseling interventions should be developed to improve attitude toward cancer among FDRs of cancer patients.

Efficacy and Safety of Innovative Experimental Chimeric Antigen Receptor (CAR) T-cells versus Axicabtagene ciloleucel (Yescarta) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma (LBCL): Matching Adjusted Indirect Comparisons (MAICs) and Systematic Review.

Despite favorable results of CAR T-cell therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL), several challenges remain, including incomplete response, immune-mediated toxicity, and antigen-loss relapse. We delineated the relative clinical benefit of the novel approaches compared to the currently approved CAR T-cell therapies. In the absence of head-to-head comparisons and randomized controlled trials, we performed Matching Adjusted Indirect Comparisons to quantify the relative efficacy and safety of experimental CARs against Axicabtagene ciloleucel (Yescarta), the first FDA-approved CAR. A total of 182 R/R LBCL patients from 15 clinical trials with individual patient data (IPD) were pooled into eight populations by their CAR T-cell constructs and +/- ASCT status. The study endpoints were Progression-Free Survival (PFS), grade ≥ 3 cytokine release syndrome (CRS), and grade ≥ 3 neurotoxicity (NT). Tandem CD19.CD20.4-1BBζ CARs indicated favorable efficacy and safety, whereas the co-infusion of CD19 & CD20 with 4-1BBζ showed no clinical benefit compared to Yescarta. Third generation CD19. CD28. 4-1BBζ, and sequential administration of autologous stem cell transplantation (ASCT) and CD19. CARs presented statistically insignificant yet improved PFS and safety except for ASCT combined intervention which had suggestively higher NT risk than Yescarta. CARs with modified co-stimulatory domains to reduce toxicity (Hu19. CD8.28Zζ and CD19. BBz.86ζ) presented remarkable safety with no severe adverse events; however, both presented worse PFS than Yescarta. Third-generation CARs demonstrated statistically significantly lower NT than Yescarta. CD20. 4-1BBζ data suggested targeting CD20 antigen alone lacks clinical or safety benefit compared to Yescarta. Further comparisons with other FDA-approved CARs are needed.

Regulation and function of H3K36 di-methylation by the trithorax-group protein complex AMC.

The Drosophila Ash1 protein is a trithorax-group (trxG) regulator that antagonizes Polycomb repression at HOX genes. Ash1 di-methylates lysine 36 in histone H3 (H3K36me2) but how this activity is controlled and at which genes it functions is not well understood. We show that Ash1 protein purified from Drosophila exists in a complex with MRG15 and Caf1 that we named AMC. In Drosophila and human AMC, MRG15 binds a conserved FxLP motif near the Ash1 SET domain and stimulates H3K36 di-methylation on nucleosomes. Drosophila MRG15-null and ash1 catalytic mutants show remarkably specific trxG phenotypes: stochastic loss of HOX gene expression and homeotic transformations in adults. In mutants lacking AMC, H3K36me2 bulk levels appear undiminished but H3K36me2 is reduced in the chromatin of HOX and other AMC-regulated genes. AMC therefore appears to act on top of the H3K36me2/me3 landscape generated by the major H3K36 methyltransferases NSD and Set2. Our analyses suggest that H3K36 di-methylation at HOX genes is the crucial physiological function of AMC and the mechanism by which the complex antagonizes Polycomb repression at these genes.

Terminalia Chebula provides protection against dual modes of necroptotic and apoptotic cell death upon death receptor ligation.

Death receptor (DR) ligation elicits two different modes of cell death (necroptosis and apoptosis) depending on the cellular context. By screening a plant extract library from cells undergoing necroptosis or apoptosis, we identified a water extract of Terminalia chebula (WETC) as a novel and potent dual inhibitor of DR-mediated cell death. Investigation of the underlying mechanisms of its anti-necroptotic and anti-apoptotic action revealed that WETC or its constituents (e.g., gallic acid) protected against tumor necrosis factor-induced necroptosis via the suppression of TNF-induced ROS without affecting the upstream signaling events. Surprisingly, WETC also provided protection against DR-mediated apoptosis by inhibition of the caspase cascade. Furthermore, it activated the autophagy pathway via suppression of mTOR. Of the WETC constituents, punicalagin and geraniin appeared to possess the most potent anti-apoptotic and autophagy activation effect. Importantly, blockage of autophagy with pharmacological inhibitors or genetic silencing of Atg5 selectively abolished the anti-apoptotic function of WETC. These results suggest that WETC protects against dual modes of cell death upon DR ligation. Therefore, WETC might serve as a potential treatment for diseases characterized by aberrantly sensitized apoptotic or non-apoptotic signaling cascades.

Brazilin selectively disrupts proximal IL-1 receptor signaling complex formation by targeting an IKK-upstream signaling components.

The ligation of interleukin-1 receptor (IL-1R) or tumor necrosis factor receptor 1 (TNFR1) induces the recruitment of adaptor proteins and their concomitant ubiquitination to the proximal receptor signaling complex, respectively. Such are upstream signaling events of IKK that play essential roles in NF-κB activation. Thus, the discovery of a substance that would modulate the recruitment of key proximal signaling elements at the upstream level of IKK has been impending in this field of study. Here, we propose that brazilin, an active compound of Caesalpinia sappan L. (Leguminosae), is a potent NF-κB inhibitor that selectively disrupts the formation of the upstream IL-1R signaling complex. Analysis of upstream signaling events revealed that brazilin markedly abolished the IL-1ß-induced polyubiquitination of IRAK1 and its interaction with IKK-γ counterpart. Notably, pretreatment of brazilin drastically interfered the recruitment of the receptor-proximal signaling components including IRAK1/4 and TRAF6 onto MyD88 in IL-1R-triggerd NF-κB activation. Interestingly, brazilin did not affect the TNF-induced RIP1 ubiquitination and the recruitment of RIP1 and TRAF2 to TNFR1, suggesting that brazilin is effective in selectively suppressing the proximal signaling complex formation of IL-1R, but not that of TNFR1. Moreover, our findings suggest that such a disruption of IL-1R-proximal complex formation by brazilin is not mediated by affecting the heterodimerization of IL-1R and IL-1RAcP. Taken together, the results suggest that the anti-IKK activity of brazilin is induced by targeting IKK upstream signaling components and subsequently disrupting proximal IL-1 receptor signaling complex formation.

Condylar positional changes up to 12 months after bimaxillary surgery for skeletal class III malocclusions.

PURPOSE: Postsurgical changes in the condylar position are of great importance to surgical stability, especially in asymmetric double-jaw surgery. The aims of this study were to evaluate positional changes of the condyle up to 12 months after surgery in patients with Class III malocclusion and to identify the factors affecting postsurgical condylar position. MATERIALS AND METHODS: The study included 33 adult patients diagnosed with skeletal Class III malocclusion who underwent bimaxillary surgery and had full cone-beam volumetric imaging (CBVI) records up to 1 year after surgery. The CBV images were obtained before surgery and 2 weeks, 3 months (T2), 6 months (T3), and 12 months after surgery. Condyles with deviated and nondeviated sides were examined separately regardless of the degree of asymmetry. Analyses of variance and multiple regression analysis were performed to identify factors that could affect the position of the mandibular condyles. RESULTS: The condyles exhibited anterior displacement at T2, which returned to a more distal position afterward in the axial view, and an inward rotation in the coronal view up to T3. From the sagittal view, the deviated and nondeviated condylar sides rotated forward and remained stable after T2. The degree of menton deviation affected the angle of condylar rotation (horizontal angle). CONCLUSION: The results of this study suggest that condyles tend to move in a certain direction, and this can influence postsurgical relapse up to 6 months after surgery. However, they remain relatively stable afterward.

PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65.

Constitutive NF-κB activation in cancer cells is caused by defects in the signalling network responsible for terminating the NF-κB response. Here we report that plant homeodomain finger protein 20 (PHF20) maintains NF-κB in an active state in the nucleus by inhibiting the interaction between PP2A and p65. We show that PHF20 induces canonical NF-κB signalling by increasing the DNA-binding activity of NF-κB subunit p65. In PHF20 overexpressing cells, the termination of tumour necrosis factor-induced p65 phosphorylation is impaired whereas upstream signalling events triggered by tumour necrosis factor are unaffected. This effect strictly depends on the interaction between PHF20 and methylated lysine residues of p65, which hinders recruitment of PP2A to p65, thereby maintaining p65 in a phosphorylated state. We further show that PHF20 levels correlate with p65 phosphorylation levels in human glioma specimens. Our work identifies PHF20 as a novel regulator of NF-κB activation and suggests that elevated expression of PHF20 may drive constitutive NF-κB activation in some cancers.

Intron-derived aberrant splicing of A20 transcript in rheumatoid arthritis.

OBJECTIVE: Aberrant splicing is one of the most significant components generating functional diversity in many pathological conditions. The objective of this study was to analyse the mutations or aberrant splicing of A20 transcript, the region encompassing the ovarian tumour (OTU) domain [which is functionally important as an inhibitor of nuclear factor (NF)-κB activation] in fibroblast-like synoviocytes (FLSs) from RA patients. METHODS: Alterations in A20 transcripts were determined through sequence analysis of 10 clones of A20 cDNA in FLSs from each of the five RA patients. The levels of aberrant A20 transcript were measured by quantitative real-time RT-PCR with primers to specifically recognize the inserted introns. The functional role of A20 and its aberrant variants were examined by analysing NF-κB luciferase reporter activity and NF-κB-dependent target gene expression. RESULTS: In RA FLSs, we discovered four novel aberrant A20 transcripts, most of which resulted from insertion of partial intron 2, intron 4 and/or deletion of exon 4. In each of these FLSs, sequence analysis revealed that these aberrant insertional sequences were flanked by consensus splice donor and acceptor sequences without nucleotide substitution, suggesting alternative splicing as the likely mutational mechanism. These variants elicited a codon frame shift by creating a premature translational stop codon, and eventually, disruption of the OTU domain (which is functionally important as an inhibitor of NF-κB activation) of A20. The expression level of aberrant A20 transcript was correlated well with persisitently enhanced status of NF-κB signalling, as evident by the phosphorylation of inhibitor of NF-κB (IκB)-α and transcription of NF-κB target genes. CONCLUSION: The results suggest that A20 inactivation by the novel aberrant splicing may contribute to RA progression by inducing persistent NF-κB activation.

Single-port access total laparoscopic hysterectomy for large uterus.

BACKGROUND/AIMS: To evaluate the feasibility and safety of single-port access total laparoscopic hysterectomy (SPA-TLH) for large uterus (>500 g). METHODS: A prospective data collection was performed in 21 consecutive patients in March 2010 and August 2011. Surgical outcome including operative time (OT) and estimated blood loss (EBL) were analyzed. RESULTS: SPA-TLH procedures were successfully performed in 16 cases (76.2%). Of the 5 failed cases, 4 were converted to multiport TLH because of distorted uterine contours and pelvic adhesions and 1 was converted to laparotomy for bleeding control. The median OT, uterine weight, and EBL were 110 (65-165) min, 600 (502-980) g, and 200 (100-800) ml, respectively. Spearman's correlation analysis demonstrated that OT and blood loss increased with increasing uterine weight (p = 0.003 and p = 0.033, respectively). No operative complications were observed during the hospital stay and 3-month follow-up following discharge. CONCLUSION: SPA-TLH for large uterus is a feasible and safe technique.

Sulfation of buprenorphine, pentazocine, and naloxone by human cytosolic sulfotransferases.

Buprenorphine, pentazocine, and naloxone are opioid drugs used for the treatment of pain and opioid dependence or overdose. Sulfation as catalyzed by the cytosolic sulfotransferases (SULTs) is involved in the metabolism of a variety of xenobiotics including drug compounds. Sulfation of opioid drugs has not been well investigated. The current study was designed to examine the sulfation of three opioid drugs, buprenorphine, pentazocine, and naloxone, in HepG2 human hepatoma cells and to identify the human SULT(s) responsible for their sulfation. Analysis of the spent media of HepG2 cells, metabolically labeled with [(35)S]sulfate in the presence of each of the three opioid drugs, showed the generation and release of their [(35)S]sulfated derivatives. A systematic analysis using eleven known human SULTs revealed SULT1A3 and SULT2A1 as the major responsible SULTs for the sulfation of, respectively, pentazocine and buprenorphine; whereas three other SULTs, SULT1A1, SULT1A2, and SULT1C4, were capable of sulfating naloxone. Enzymatic assays using combinations of these opioid drugs as substrates showed significant inhibitory effects in the sulfation of buprenorphine and pentazocine by naloxone. Differential sulfating activities toward the three opioid drugs were detected in cytosol or S9 fractions of human lung, liver, kidney, and small intestine. Collectively, these results imply that sulfation may play a role in the metabolism of buprenorphine, pentazocine, and naloxone in vivo.

Selective plantar fascia release for nonhealing diabetic plantar ulcerations.

BACKGROUND: Achilles tendon lengthening can decrease plantar pressures, leading to resolution of forefoot ulceration in patients with diabetes mellitus. However, this procedure has been reported to have a complication rate of 10% to 30% and can require a long period of postoperative immobilization. We have developed a new technique, selective plantar fascia release, as an alternative to Achilles tendon lengthening for managing these forefoot ulcers. METHODS: We evaluated sixty patients with diabetes for a mean of 23.5 months after selective plantar fascia release for the treatment of nonhealing diabetic neuropathic ulcers in the forefoot. Preoperative and postoperative dorsiflexion range of motion of the affected metatarsophalangeal joint and wound-healing data were used to evaluate the effectiveness of the procedure and to determine the relationship between plantar fascia release and ulcer healing. Complications were recorded. RESULTS: Thirty-six (56%) of the ulcers healed within six weeks, including twenty-nine (60%) of the plantar toe ulcers and seven (44%) of the metatarsophalangeal joint ulcers. The mean range of motion of the affected metatarsophalangeal joint increased from 15.3° ± 7.8° to 30.6° ± 14.1° postoperatively (p < 0.05). All patients in whom the preoperative dorsiflexion of the affected metatarsophalangeal joint was between 5° and 30° and in whom the range of motion of that joint increased by ≥13° after the procedure experienced healing of the ulcer. No ulcer recurrence in the original location was identified during follow-up. No patients experienced any complications associated with the selective plantar fascia release. CONCLUSIONS: Our results suggest that selective plantar fascia release can lead to healing of neuropathic plantar forefoot ulcers in diabetic patients. Ulcers in patients in whom the preoperative dorsiflexion angle of the affected metatarsophalangeal joint is between 5° and 30° and in whom the increase in range of motion is ≥13° postoperatively have the greatest chance of being cured. LEVEL OF EVIDENCE: Therapeutic level IV. See Instructions for Authors for a complete description of the levels of evidence.