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Introduction: Intravenous (IV) lidocaine has been used as a transitional treatment in headache and facial pain conditions, typically as an inpatient infusion over several days, which is costly and may increase the risk of adverse effects. Here we report on our experience using a single one-hour IV lidocaine infusion in an outpatient day-case setting for the management of refractory primary headache disorders with facial pain and trigeminal neuralgia. Methods: This is a retrospective, single-center analysis on patients with medically refractory headache with facial pain and trigeminal neuralgia who were treated with IV lidocaine between March 2018 and July 2022. Lidocaine 5 mg.kg-1 in 60 mL saline was administered over 1 h, followed by an observation period of 30 min. Patients were considered responders if they reported reduction in pain intensity and/or headache frequency of 50% or greater. Duration of response was defined as short-term (< 2 weeks), medium-term (2-4 weeks) and long-term (> 4 weeks). Results: Forty infusions were administered to 15 patients with trigeminal autonomic cephalalgias (n = 9), chronic migraine (n = 3) and trigeminal neuralgia (n = 3). Twelve patients were considered responders (80%), eight of whom were complete responders (100% pain freedom). The average duration of the treatment effect for each participant was 9.5 weeks (range 1-22 weeks). Six out of 15 patients reported mild and self-limiting side effects (40%). Conclusion: A single infusion of IV lidocaine might be an effective and safe transitional treatment in refractory headache conditions with facial pain and trigeminal neuralgia. The sustained effect of repeated treatment cycles in some patients may suggest a role as long-term preventive therapy in some patients.
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Spin-valley locking in monolayer transition metal dichalcogenides has attracted enormous interest, since it offers potential for valleytronic and optoelectronic applications. Such an exotic electronic state has sparsely been seen in bulk materials. Here, we report spin-valley locking in a Dirac semimetal BaMnSb2. This is revealed by comprehensive studies using first principles calculations, tight-binding and effective model analyses, angle-resolved photoemission spectroscopy measurements. Moreover, this material also exhibits a stacked quantum Hall effect (QHE). The spin-valley degeneracy extracted from the QHE is close to 2. This result, together with the Landau level spin splitting, further confirms the spin-valley locking picture. In the extreme quantum limit, we also observed a plateau in the z-axis resistance, suggestive of a two-dimensional chiral surface state present in the quantum Hall state. These findings establish BaMnSb2 as a rare platform for exploring coupled spin and valley physics in bulk single crystals and accessing 3D interacting topological states.
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Insulin-like growth factor binding protein 5 (IGFBP5) is broadly bioactive, but its role in osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) remains to be clarified. Here, we demonstrated that IGFBP5 expression was markedly increased during the early osteogenic differentiation of hMSCs. We then over-expressed and knocked down this gene in hMSCs and evaluated the impact of manipulation of IGFBP5 expression on osteogenic differentiation based upon functional assays, ALP staining, and expression of osteogenic markers. Together, these analyses revealed that IGFBP5 over-expression enhanced early osteogenic differentiation, as evidenced by increased ALP staining and osteogenic marker induction, whereas knocking down this gene impaired the osteogenic process. Over-expression of IGFBP5 also markedly bolstered the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation level, while IGFBP5 knockdown suppressed this signalling activity. We additionally compared the impact of simultaneous IGFBP5 overexpression and ERK1/2 inhibitor treatment to the effect of IGFBP5 over-expression alone in these hMSCs, revealing that small molecule-mediated EKR1/2 inhibition was sufficient to impair osteogenic differentiation in the context of elevated IGFBP5 levels. These findings indicated that IGFBP5 drives the early osteogenic differentiation of hMSCs via the ERK1/2 signalling pathway. Our results offer value as a foundation for future efforts to study and treat serious bone-related diseases including osteoporosis.
Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Cell Differentiation , Cells, Cultured , Humans , Insulin-Like Growth Factor Binding Protein 5/genetics , Insulin-Like Growth Factor Binding Protein 5/metabolism , Mesenchymal Stem Cells/metabolism , Signal TransductionABSTRACT
Objective: To study the safety and feasibility of total hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and transumbilical laparoendoscopic single site surgery (TU-LESS). Methods: The study was a retrospective cohort analysis. In West China Second University Hospital, from October 1, 2018 to June 30, 2019, the patients with an indication for hysterectomy due to benign uterine diseases were enrolled, and were grouped by the surgical procedure. Various post-operative surgical outcomes, including the success rate of operation, uterine volume, operative time, blood loss, intraoperative complications, postoperative complications, the first time of flatus, the preserved time of catheter after operation, and the length of hospitalization were measured. The data were assessed by the software of SPSS. Results: Totally 30 patients were included in the vNOTES group, and 77 patients were included in the TU-LESS group, all of the procedures were completed successfully without conversion to traditional multiport laparoscopy or laparotomy. Non differences were observed between two groups, including uterine volume [(165±36) vs (235±38) cm3, P=0.243], operation time [(150±41) vs (169±48) minutes, P=0.063], blood loss [(54±15) vs (54±14) ml, P=0.985], the rate of intraoperative complications [3% (1/30) vs 4% (2/77), P=1.000], the rate of postoperative complications [13% (4/30) vs 4% (3/77), P=0.095] and the rate of bilateral salpingo-oophorectomy [50% (15/30) vs 31% (24/77), P=0.069]. Patients in the vNOTES group had significantly less recovery time of intestine function [(1.7±0.5) vs (2.3±0.6) days, P=0.001], shorter time of indwelling catheter [(1.9±0.4) vs (2.3±0.6) days, P=0.004], and duration of hospitalization [(3.2±0.8) vs (3.6±0.9) days, P=0.045]. Conclusions: vNOTES and TU-LESS are both safe and feasible for total hysterectomy. Compared with TU-LESS, vNOTES may be a promising approach with earlier recovery, less injury and better cosmetic.
Subject(s)
Endoscopy , Hysterectomy/methods , Laparoscopy , Natural Orifice Endoscopic Surgery/methods , Uterine Diseases/surgery , China , Cohort Studies , Feasibility Studies , Female , Humans , Hysterectomy/adverse effects , Natural Orifice Endoscopic Surgery/adverse effects , Operative Time , Retrospective Studies , Treatment Outcome , Uterine Diseases/diagnosisABSTRACT
To introduce current literature reporting situations of the off-label drug use(OLDU) by analyzing relevant literatures published in China, this study comprehensively focused on literatures about OLDU in China in seven Chinese and English databases, then extracted and analyzed the data by different literature types. A total of 667 papers were analyzed. The number of literatures about OLDU data analyzed in hospitals was 325, and the number of clinical studies relating to OLDU was 329, in which case series and case reports were the majority(69.91%). In addition, there were 13 expert consensuses of OLDU and another 56 studies about drug use based on the real-world data characteristics and influencing factors. The number of OLDU data studies has increased year by year. Based on the existing studies, there were more western medicine reports than traditional Chinese medicines, and OLDU types were mainly for over-dosage use. The literatures from OLDU data in hospital were mostly limited to one or several tertiary hospitals in a certain area, and the OLDU types were not uniform. Clinical studies were mainly clinical control trials and case series/reports, but with contradictory reporting results. There were fewer OLDU consensus, and the recommended classification was not uniform. The characteristics and analysis of influencing factors of drug using data in real-world focused on traditional Chinese medicine injections, and the results were not the same. In the future, we shall pay more attention to and strengthen reporting and analysis of OLDU, define study objectives, and unify the content and reporting standards, so as to promote the integrated utilization of OLDU data and reflect real situations in our country.
Subject(s)
Drug Labeling , Off-Label Use , China , Consensus , Medicine, Chinese TraditionalABSTRACT
Auditory hair cells receive olivocochlear efferent innervation, which refines tonotopic mapping, improves sound discrimination, and mitigates acoustic trauma. The olivocochlear synapse involves α9α10 nicotinic acetylcholine receptors (nAChRs), which assemble in hair cells only coincident with cholinergic innervation and do not express in recombinant mammalian cell lines. Here, genome-wide screening determined that assembly and surface expression of α9α10 require ligand binding. Ion channel function additionally demands an auxiliary subunit, which can be transmembrane inner ear (TMIE) or TMEM132e. Both of these single-pass transmembrane proteins are enriched in hair cells and underlie nonsyndromic human deafness. Inner hair cells from TMIE mutant mice show altered postsynaptic α9α10 function and retain α9α10-mediated transmission beyond the second postnatal week associated with abnormally persistent cholinergic innervation. Collectively, this study provides a mechanism to link cholinergic input with α9α10 assembly, identifies unexpected functions for human deafness genes TMIE/TMEM132e, and enables drug discovery for this elusive nAChR implicated in prevalent auditory disorders.
Subject(s)
Deafness/metabolism , Hair Cells, Auditory/metabolism , Membrane Proteins/metabolism , Receptors, Nicotinic/metabolism , Animals , Cochlea/metabolism , Deafness/genetics , Humans , Ligands , Membrane Proteins/genetics , Mice , Protein Binding , Receptors, Nicotinic/genetics , Synapses/metabolismABSTRACT
The research studied the effects of l-methionine (l-Met) on growth performance, carcass quality, feather traits, and small intestinal morphology of Pekin ducks compared with conventional dl-methionine (dl-Met). A total of 1080, 1-day-old male Pekin ducks were randomly allotted to 9 groups with 6 replicate pens of 20 birds each. During the starter phase (1 to 14 d), ducks were fed a basal diet (Met, 0.30%) or that supplemented with dl-Met or l-Met at 0.05, 0.10, 0.15, or 0.20% of feed. During the grower phase (15 to 35 d), ducks were fed a basal diet (Met, 0.24%) or that supplemented with dl-Met or l-Met at 0.04, 0.08, 0.12, or 0.16% of feed. Compared with ducks fed the basal diet, supplementation with either dl-Met or l-Met increased the body weight (BW) of ducks at days 14 and 35, increased average daily gain (ADG) and average daily feed intake (ADFI), decreased F:G at the starter phase, and increased ADG over the whole 35-d period (P < 0.05). The efficacy of l-Met compared to dl-Met was 140.1% for 14-d BW, 137.6% for ADG and 121.0% for F:G for days 1 to 14. Ducks fed diets supplemented with l-Met had greater proportion of leg muscle, higher than in ducks provided with dl-Met (P < 0.05). The breast muscle proportion was enhanced with dl-Met rather than l-Met supplementation (P < 0.01). The back feathers score and fourth primary wing feather length were increased with dl-Met or l-Met supplementation (P < 0.01), and there was increased efficacy of l-Met relative to dl-Met for back feathers score (153.1%). Dietary dl-Met or l-Met supplementation increased villus height of ileal mucosa of ducks at days 14 and 35 (P < 0.01). Overall, dietary l-Met or dl-Met supplementation affected the growth performance of ducks during the starter phase, and improved the feather traits and small intestinal morphology. The efficacy of l-Met to dl-Met ranged from 120 to 140% for growth performance of young ducks (1 to 14 d) and was 153% for the feather traits of ducks (35 d).
Subject(s)
Ducks/physiology , Feathers/physiology , Intestine, Small/anatomy & histology , Meat/analysis , Methionine/metabolism , Animal Feed/analysis , Animals , Diet/veterinary , Dietary Supplements/analysis , Dose-Response Relationship, Drug , Ducks/growth & development , Male , Methionine/administration & dosage , Methionine/classification , Random AllocationABSTRACT
PURPOSE: Clear-cell renal cell carcinoma (ccRCC) is characterized by genetic abnormalities, while the role of Guanine Nucleotide-Binding Protein Beta 1 (GNB1) in ccRCC has not been studied. We thus aimed to evaluate the expression and prognostic value of GNB1 in ccRCC. METHODS: A two-stage study (exploration and validation) was conducted using in silico and immunohistochemical (IHC) scoring of ccRCC samples from our institute, to evaluate the association between GNB1 expression and clinicopathological parameters of ccRCC patients. Pathway analyses were performed for genes coexpressed with GNB1 using the KOBAS platform to profile the function of GNB1 and IHC validation. RESULTS: In the exploration stage, data from TCGA ccRCC dataset were reproduced, which contained 537 patients with ccRCC and found that downregulation of GNB1 was significantly associated with worse prognosis. IHC staining from the Human Protein Atlas showed significantly downregulation of GNB1 in ccRCC tissue compared with normal kidney. Pathway analysis showed significantly altered vascular endothelial growth factor (VEGF) signaling pathways among which expressions of 3 genes (WASF2, NRP1, and HIP1) were significantly associated with GNB1 expression, respectively. In the validation stage, included were 80 ccRCC samples and GNB1 expression was scored using IHC positivity. GNB1 expression was negatively associated with tumor stage, lymph node invasion, metastasis, older age, and increased tumor grade. Female gender and receiving neoadjuvant therapy were also associated with decreased GNB1 expression. The expressions of WASF2, NRP1 and HIP1 were also studied and found that they were significantly associated with GNB1. CONCLUSION: GNB1 was downregulated in ccRCC. Decreased GNB1 expression was associated with worsened disease characteristics and prognosis. GNB1 was related with VEGF signaling in ccRCC, implying a therapeutic potential of this factor.
Subject(s)
Carcinoma, Renal Cell/genetics , GTP-Binding Protein beta Subunits/genetics , Vascular Endothelial Growth Factor A/genetics , Carcinoma, Renal Cell/pathology , Down-Regulation , Female , GTP-Binding Protein beta Subunits/metabolism , Humans , Male , Middle Aged , Prognosis , Signal TransductionABSTRACT
ããPurpose Our objective was to evaluate the birth outcomes of FET from different developmental stage of embryo at freezing (Day 3, Day 5 and Day 6). Methods All vitrified-warmed day 3 (D3) and day 5/6 (D5, D6) embryo transfers during the time period from January 2013 until December 2015 were included in the study. The Birthweight, Low birthweight (LBW), sexual distinction, gestation and for singleton births and twins conceived by FET were compared retrospectively between three cryopreservation strategies utilizing either D3, D5 or D6 embryo freezing. All embryos were vitrified by Dimethylsulfoxide (DMSO), Ethylene glycol (EG) and Sucrose used as Cryoprotectants and using Cryoleaf as the receptacles. Results A total of 993 infants from 771 women. The length of embryos storage was 3-38 months, with a median of 8 months. For singleton, birthweight from D5 and D6 blastocysts transfers were signiï¬cantly heavier than for D3 cleavage-stage embryos transfers (P =0.0065 P =0.0006). For twins, birthweight from D6 blastocysts transfers were significantly heavier than for D5 blastocysts transfers (P =0.0044), and children born after D3 were at a signigicantly increased risk of being born a LBW. Conclusions Birthweights from FET are influenced by developmental stage of embryos at freezing, which were lower for cleavage-stage embryos transfer than blastocysts transfer after FET in singletons. The birth rate of LBW infants was higher in the twins. The study was small so there may be other factors than cryopreservation which affected outcomes. A higher sample size or a multi-centre prospective randomized design could be used in future studies to corroborate the current ï¬ndings.
Subject(s)
Cryopreservation/methods , Embryo Transfer/methods , Embryonic Development , Freezing , Live Birth , Pregnancy Outcome , Adult , Birth Weight , Female , Humans , Infant, Newborn , Male , Pregnancy , Prospective Studies , Retrospective Studies , Twins , VitrificationABSTRACT
Endoscopic surgery is increasingly used for early gastric cancer (EGC) treatment worldwide, and lymph node metastasis remains the most important risk factor for endoscopic surgery in EGC patients. Olfactomedin 4 (OLFM4) is mainly expressed in the digestive system and upregulated in several types of tumors. However, the role of OLFM4 in EGC has not been explored. We evaluated OLFM4 expression by immunohistochemical staining in 105 patients with EGC who underwent gastrectomy. The clinicopathological factors and OLFM4 expression were co-analyzed to predict lymph node metastasis in EGC. The metastatic mechanism of OLFM4 in gastric cancer was also investigated. We found that OLFM4 was upregulated in EGC tumor sections, and relatively low expression of OLFM4 was observed in patients with lymph node metastasis. OLFM4 expression as well as tumor size and differentiation were identified as independent factors, which could be co-analyzed to generate a better model for predicting lymph node metastasis in EGC patients. In vitro studies revealed that knockdown of OLFM4 promoted the migration of gastric cancer cells through activating the NF-κB/interleukin-8 axis. Negative correlation between OLFM4 and interleukin-8 expression was also observed in EGC tumor samples. Our study implies that OLFM4 expression is a potential predictor of lymph node metastasis in EGC, and combing OLFM4 with tumor size and differentiation could better stratify EGC patients with different risks of lymph node metastasis.
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OBJECTIVE: To explore the effect and significance of tumor necrosis factor-α( TNF-α) in serum and bronchoalveolar lavage fluid( BALF) of coal workers' pneumoconiosis( CWP). METHODS: Twenty-eight cases of CWP were selected by purposive sampling method and divided into 3 groups based on different stages of pneumoconiosis. There were 7 cases in stage Ⅰ,10 cases in stage Ⅱ,and 11 cases in stage Ⅲ. The venous blood and BALF were collected.TNF-α in the serum and BALF were detected by chemiluminescence assay. The lung function was determined. RESULTS: In the serum,the TNF-α level of CWP patients was positively correlated with the CWP stage [Spearman correlation coefficient( rS) = 0. 843,P < 0. 01],and negatively correlated with the forced expiratory volume in one second/forced vital capacity( FEV1/ FVC)( rS=- 0. 503,P < 0. 01). In BALF,the TNF-α level of CWP patients was negatively correlated with the CWP stage( rS=- 0. 654,P < 0. 01),and positively correlated with the FEV1/ FVC( rS= 0. 432,P <0. 05). The TNF-α level in the serum was negatively correlated with the TNF-α level in BALF( rS=- 0. 561,P < 0. 01).CONCLUSION: With the development of pneumoconiosis,the levels of TNF-α in the serum and BALF showed different variation,and were correlated with the changes of FEV1/ FVC. The level of TNF-α could be used as a reference index for evaluating the severity of CWP.
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The Wnt pathway has been implicated in the initiation, progression, and metastasis of lung cancer. T cell factor 4, a member of TCF/LEF family, acts as a transcriptional factor for Wnt pathways in lung cancer. Increasing amounts of evidence have shown that TCF-4 has multiple alternative splicing isoforms with transactivation or transrepression activity toward the Wnt pathway. Here, we found the presence of multiple TCF-4 isoforms in lung cancer cell lines and in normal bronchial epithelial cells. TCF-4K isoform expression was significantly decreased in lung cancer cells compared with normal bronchial epithelial cells and was identified as a transcriptional suppressor of the Wnt pathway in non-small cell lung carcinoma (NSCLC). Overexpression of TCF-4K significantly inhibited the proliferation and migration of NSCLC cells. Collectively, our data indicate that TCF-4K functions as a tumor suppressor in NSCLC by down-regulating the Wnt pathway.
Subject(s)
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Transcription Factors/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/biosynthesis , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Bronchi/cytology , Bronchi/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Cloning, Molecular , Down-Regulation , Epithelial Cells/cytology , Epithelial Cells/metabolism , Humans , Lung Neoplasms/genetics , Neoplasm Metastasis , Protein Isoforms , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription Factor 4 , Transcription Factors/biosynthesis , Transcription Factors/genetics , Wnt Signaling Pathway/geneticsABSTRACT
Diabetes mellitus (DM) is currently known to be one of the risk factors for pulmonary tuberculosis (PTB) and the proportion of DM in PTB is rising along with the increased prevalence of DM in countries with high PTB burden. This study was designed to explore the impact of DM on clinical presentation and treatment outcome of PTB in China. In an urban setting in Beijing, 1126 PTB patients, 30·6% with positive sputum smear, registered in two PTB dispensaries from January 2010 to December 2011 were screened for DM and were followed up prospectively during PTB treatment. DM was observed in 16·2% of patients with PTB. PTB with DM appeared to be associated with older age and a higher proportion of re-treatment. On presentation, DM was associated with more severe PTB signs with higher proportions of smear positivity [odds ratio (OR) 2·533, 95% confidence interval (CI) 1·779-3·606], cavity (OR 2·253, 95% CI 1·549-3·276) and more symptoms (OR 1·779, 95% CI 1·176-2·690). DM was also associated with non-TB deaths (OR 5·580, 95% CI 2·182-14·270, P < 0·001) and treatment failure (OR 6·696, 95% CI 2·019-22·200, P = 0·002). In Beijing, the findings of this study underlined the need to perform early bi-directional screening programmes and explore the underlying mechanism for different treatment outcomes for PTB with DM.
Subject(s)
Antitubercular Agents/therapeutic use , Diabetes Complications , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/pathology , Adult , China , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Survival Analysis , Treatment Outcome , Tuberculosis, Pulmonary/epidemiology , Urban Population , Young AdultABSTRACT
AIMS: Soft tissue sarcomas are uncommon, but relatively aggressive tumours. Although surgical resection remains the primary therapeutic modality for all localised tumours, brachytherapy combined with function-preserving excision is a popular treatment for extremity soft tissue sarcomas. The objective of this study was to evaluate the effect of interstitial permanent brachytherapy using I(125) seeds in patients undergoing the combined modality in the management of soft tissue sarcomas at our institution. MATERIALS AND METHODS: Between January 2007 and January 2012, 110 adult patients aged 18-86 years (median = 44 years) with extremity soft tissue sarcomas and who underwent interstitial permanent brachytherapy as part of the local treatment were included in this study. Treatment included wide local excision of the tumour and brachytherapy using a permanent I(125) implantation. Complications were assessed in terms of wound complication and peripheral nerve damage. RESULTS: After a median follow-up of 43.7 months, the local control, disease-free survival and overall survival for the entire cohort studied were 74, 54 and 77%, respectively. The actual rates of wound complications requiring reoperation and nerve damage were 4.5 and 1.8%, respectively. CONCLUSIONS: We conclude that interstitial permanent brachytherapy with I(125) after function-preserving surgery results in a satisfactory outcome in patients with extremity soft tissue sarcomas and the complication rate is low.
Subject(s)
Brachytherapy/methods , Iodine Radioisotopes/administration & dosage , Sarcoma/radiotherapy , Soft Tissue Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Disease-Free Survival , Extremities/pathology , Extremities/radiation effects , Female , Humans , Male , Middle Aged , Radiotherapy Dosage , Sarcoma/pathology , Soft Tissue Neoplasms/pathology , Young AdultABSTRACT
The complex wound with the exposed hardware and infection is one of the common complications after the internal fixation of the tibia fracture. The salvage of hardware and reconstruction of soft tissue defect remain challenging. In this report, we presented our experience on the use of the distally based saphenous neurocutaneous perforator flap combined with vacuum-assisted closure (VAC) therapy for the coverage of the soft tissue defect and the exposed hardware in the lower extremity with fracture. Between January 2008 and July 2010, seven patients underwent the VAC therapy followed by transferring a reversed saphenous neurocutaneous perforator flap for reconstruction of the wound with exposed hardware around the distal tibia. The sizes of the flaps ranged from 6 × 3 cm to 15 × 6 cm. Six flaps survived completely. Partial necrosis occurred in one patient. There were no other complications of repair and donor sites. Bone healing was achieved in all patients. In conclusion, the reversed saphenous neurocutaneous perfortor flaps combined with the VAC therapy might be one of the options to cover the complex wound with exposed hardware in the lower extremities.
Subject(s)
Fracture Fixation, Internal , Limb Salvage/methods , Negative-Pressure Wound Therapy , Perforator Flap/innervation , Staphylococcal Infections/surgery , Surgical Wound Infection/surgery , Tibial Fractures/surgery , Adult , Aged , Female , Follow-Up Studies , Fracture Fixation, Internal/instrumentation , Humans , Male , Middle Aged , Orthopedic Fixation Devices , Treatment Outcome , Wound HealingABSTRACT
It has been demonstrated that ischemic postconditioning (IPO) is capable of attenuating ischemia/reperfusion (I/R) injury in the heart. However, the novel role of pharmacological postconditioning in the liver remains unclear. In this study, the hypothesis that diazoxide postconditioning reduces I/R-induced injury in rat liver was tested. Rats were assigned randomly to the sham-operated control, I/R (occlusion of the porta hepatis for 60 min, followed by a persistent reperfusion for 120 min), diazoxide ischemic postconditioning (DIPO; occlusion of the porta hepatis for 60 min, then treatment with diazoxide for 10 min reperfusion, followed by a persistent reperfusion for 110 min) or 5-hydroxydecanoate (5-HD)+DIPO (occlusion of the porta hepatis for 60 min, then treatment with diazoxide and 5-HD for 10 min reperfusion, followed by a persistent reperfusion for 110 min) groups. The alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were assayed. The expression levels of protein kinase c-ε (pkc-ε), cytochrome c (cyt-c), caspase-3 and bcl-2 protein were determined by western blotting. The serum levels of ALT and AST and expression levels of cyt-c and caspase-3 were significantly lower in the DIPO group (P<0.05). However, the protein expression levels of pkc-ε and bcl-2 were markedly increased in the DIPO group (P<0.05). 5-HD abrogated the protective effects of DIPO. The data of the present study provide the first evidence that DIPO protects the liver from I/R injury by opening the mitochondrial KATP channels, activating and upregulating pkc-ε and inhibiting the activation of the apoptotic pathway by decreasing the release of cyt-c and the expression of caspase-3 and increasing bcl-2 expression.
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OBJECTIVES: To evaluate care provided by primary care physicians in community practice to older patients presenting with cognitive impairment and dementia. DESIGN: Secondary analysis of an intervention study. SETTING: Primary care clinics. PARTICIPANTS: 101 patients 75 years and older enrolled in the ACOVE-2 study who presented with a new cognitive problem, new dementia, or prevalent dementia. MEASUREMENTS: Patients assessment and management were evaluated from medical record review and caregiver interviews. RESULTS: Among 34 patients presenting with a new cognitive problem, half received a cognitive assessment comprising of a test of memory and one other cognitive task, 41% were screened for depression and 29% were referred to a consultant. Of the 27 patients with newly diagnosed dementia, 15% received the components of a basic neurological examination, one-fifth received basic laboratory testing and for one third the medical record reflected an attempt to classify the type of dementia. Counseling was under-reported in the medical record compared to the caregiver interview for the 101 patients with dementia, but even the interview revealed that about half or fewer patients received counseling about safety and accident prevention, caregiver support or managing conflicts. Less than 10% were referred to a social worker. CONCLUSION: This small but detailed evaluation suggests patients presenting with cognitive problems to primary care physicians do not consistently receive basic diagnosis and management.
Subject(s)
Cognition Disorders , Dementia , Health Services for the Aged/standards , Patient Care Management/standards , Practice Patterns, Physicians'/standards , Primary Health Care/standards , Quality of Health Care/standards , Aged , Aged, 80 and over , Caregivers , Cognition , Cognition Disorders/diagnosis , Community Health Services/standards , Counseling , Dementia/classification , Dementia/diagnosis , Depression/diagnosis , Female , Geriatric Assessment , Humans , Interviews as Topic , Male , Medical Records , Memory , Memory Disorders/diagnosis , Referral and ConsultationABSTRACT
BACKGROUND AND STUDY AIMS: The use of natural oriï¬ce transluminal endoscopic surgery (NOTES) for gastroenterostomy has been previously reported, but it remains technically challenging and additional assistance is often needed. The aim of this study was to develop and evaluate a novel method for the creation of a gastroenterostomy using NOTES with an occluder. METHODS: Transgastric endoscopic gastroenterostomy was performed in 12 healthy female dogs using a therapeutic upper gastrointestinal endoscope and a partially covered occluder. The occluder was removed with a snare 1 week later. The patency of the gastroenterostomy was confirmed by endoscopy, contrast radiological study, necropsy, and histological examination after 2 weeks. RESULTS: NOTES gastroenterostomy with an occluder was successful in all 12 dogs. The mean operative time was 32.3 ± 10.3 min (range 20.3 - 53.5). One dog (the first; 8.3 %) died 4 days after the operation of severe intra-abdominal infection due to incorrect deployment of the occluder and poor bowel preparation. Minor bleeding occurred at the anastomosis after removal of the occluder in two of the remaining dogs (18.2 %). Necropsy revealed postoperative adhesions that had developed at the anastomotic site in one dog (9.1 %). No anastomotic leakage or intestinal obstruction was observed. Complete healing of the anastomosis was confirmed on histological evaluation. CONCLUSION: Gastroenterostomy performed entirely by NOTES using an occluder was technically feasible in this survival animal model.