Spectrum and antibiotic sensitivity of bacterial keratitis: a retrospective analysis of eight years in a Tertiary Referral Hospital in Southwest China.

Purpose: The objective of this study was to investigate the epidemiological characteristics, distribution of isolates, prevailing patterns, and antibiotic susceptibility of bacterial keratitis (BK) in a Tertiary Referral Hospital located in Southwest China. Methods: A retrospective analysis was conducted on 660 cases of bacterial keratitis occurring between January 2015 and December 2022. The demographic data, predisposing factors, microbial findings, and antibiotic sensitivity profiles were examined. Results: Corneal trauma emerged as the most prevalent predisposing factor, accounting for 37.1% of cases. Among these cases, bacterial culture results were positive in 318 cases, 68 species of bacteria were identified. The most common Gram-Positive bacteria isolated overall was the staphylococcus epidermis and the most common Gram-Negative bacteria isolated was Pseudomonas aeruginosa. Methicillin-Resistant Staphylococci accounted for 18.1% of all Gram-Positive bacteria. The detection rate of P. aeruginosa showed an increasing trend over time (Rs=0.738, P=0.037). There was a significant decrease in the percentage of Gram-Negative microorganisms over time (Rs=0.743, P=0.035). The sensitivity of Gram-Positive bacteria to linezolid, vancomycin, tigecycline, quinupristin/dalfopristin, and rifampicin was over 98%. The sensitivity rates of Gram-Negative bacteria to amikacin, meropenem, piperacillin/tazobactam, cefoperazone sodium/sulbactam, ceftazidime, and cefepime were all above 85%. In patients with a history of vegetative trauma, the possibility of BK should be taken into account in addition to the focus on fungal keratitis. Conclusion: The microbial composition primarily consists of Gram-Positive cocci and Gram-Negative bacilli. Among the Gram-Positive bacteria, S. epidermidis and Streptococcus pneumoniae are the most frequently encountered, while P. aeruginosa is the predominant Gram-Negative bacteria. To combat Gram-Positive bacteria, vancomycin, linezolid, and rifampicin are considered excellent antimicrobial agents. When targeting Gram-Negative pathogens, third-generation cephalosporins exhibit superior sensitivity compared to first and second-generation counterparts. As an initial empirical treatment for severe cases of bacterial keratitis and those unresponsive to fourth-generation fluoroquinolones in community settings, the combination therapy of vancomycin and tobramycin is a justifiable approach. Bacterial keratitis can be better managed by understanding the local etiology and antibacterial drug susceptibility patterns.

Prevalence and clinical implications of polypharmacy and potentially inappropriate medication in elderly patients with heart failure: results of six months' follow-up.

OBJECTIVES: To investigate the prevalence of polypharmacy and potentially inappropriate medication (PIM) in elderly patients with heart failure (HF) and their impact on readmission and mortality. METHODS: We conducted a study of 274 participants aged 60 years or older with HF. The prevalence of polypharmacy (defined as the use of five or more medications) was calculated, and the 2019 American Geriatrics Society Beers criteria were applied to access PIMs. Medications and PIMs were characterized at admission and discharge, and changes in prescriptions during hospitalization were compared. The impact of polypharmacy and PIM on readmission and mortality were investigated. RESULTS: The median age of this study population was 68 years old. The median number of prescribed drugs was 7 at admission and 10 at discharge. At discharge, 99.27% of all patients were taking five or more drugs. The incidence of composite endpoint and cardiovascular readmission increased with the number of polypharmacy within 6 months. The use of guideline-directed medical therapy reduced the incidence of composite endpoint events and cardiovascular readmission, while the use of non-cardiovascular medications increased the composite endpoint events. The frequency of PIMs was 93.79% at discharge. The incidence of composite endpoint events increased with the number of PIMs. "PIMs in older adults with caution" increased cardiovascular readmission and "PIMs based on kidney function" increased cardiovascular mortality. Several comorbidities were associated with cardiovascular mortality or non-cardiovascular readmission. CONCLUSIONS: Polypharmacy and PIM were highly prevalent in elderly patients with HF, and their use was associated with an increased risk of composite endpoint events, readmission and mortality. Non-cardiovascular medications, "PIMs in older adults with caution", "PIMs based on kidney function" and several comorbidities were important factors associated with hospital readmission and mortality. Our findings highlight the importance of medication optimization in the management of HF in elderly patients.

Migrating Localized ST-Segment Elevation With Ongoing Chest Pain.

A patient in their 60s presented with a 6-hour history of sudden-onset worsening chest pain associated with shortness of breath and diaphoresis. What is your diagnosis?

Sohlh2 Regulates the Stemness and Differentiation of Colon Cancer Stem Cells by Downregulating LncRNA-H19 Transcription.

Colon cancer stem cells (CSC) are tumor-initiating cells that drive tumorigenesis and progression through self-renewal and various differentiation potency. Therefore, the identification of factors critical for colon CSC function is vital for the development of therapies. Sohlh2 belongs to the superfamily of bhlh transcription factors and serves as a tumor suppressor in several tumors. The role of Sohlh2 in CSCs remains unknown. Here we demonstrated that Sohlh2 was related to the inhibition of LncRNA-H19/miR-141/ß-catenin signaling and led to the consequent suppression of colon CSC stemness and the promotion of colon CSC differentiation in vitro and in vivo. Moreover, Sohlh2 could directly bind to the promoter of LncRNA-H19 and repress its transcription activity. LncRNA-H19 mediated the effects of Sohlh2 on colon CSC stemness and differentiation. Clinically, we observed a significant inverse correlation between Sohlh2 and LncRNA-H19, ß-catenin, Lgr5, CD133 expression levels, and positive correlation between Sohlh2 and MUC2, TFF2 expression in colon cancer tissues. Collectively, our findings suggest an important role of the Sohlh2/LncRNA-H19/miR-141/ß-catenin pathway in regulating colon CSC stemness and differentiation, suggesting potential therapeutic targets for colon cancer. IMPLICATIONS: This study identifies that Sohlh2 directly manipulates LncRNA-H19 transcription and suppresses the ß-catenin signaling pathway and the Sohlh2/LncRNA-H19/miR-141/ß-catenin signaling pathway plays an essential role in the stemness of colon CSCs.

Reach-to-grasp kinematics and kinetics with and without visual feedback in early-stage Alzheimer's disease.

This study aimed to investigate the effects of early-stage Alzheimer's disease (AD) on the reach-to-grasp kinematics and kinetics with and without visual supervision of the grasping arm and hand. Seventeen patients who had been diagnosed with early-stage AD and 17 age- and gender-matched, cognitive normal (CN) adults participated in the experiment. A mirror operating system was designed to block the visual feedback of their grasping hand and forearms but to virtually show grasped targets. The target for reach-to-grasp kinematics was a reflective marker installed on a base; and the target for reach-to-grasp kinetics was a custom-made apparatus installed with two six-component force/torque transducers. Kinematics and kinetic parameters were used to quantify the reach-to-grasp performances. Results showed that the early-stage AD remarkably decreased the reaching speed, reduced the grasping accuracy and increased the transportation variability for reach-to-grasp kinematics. For kinetic analysis, early-stage AD extended the preload duration, disturbed the grip and lift forces coordination, and increased the feedforward proportion in the grasping force control. The AD-related changes in the reach-to-grasp kinematic and kinetic parameters depended on visual feedback and were associated with nervous system function according to correlation analyses with the neuropsychological testing. These results suggest that the abnormal kinematic and kinetic characteristics may correlate with the neuropsychological status of early-stage AD, and that the reach-to-grasp kinematic and kinetic maneuver could potentially be used as a novel tool for non-invasive screening or evaluation of early-stage AD.

Protection of Exogenous Phosphocreatine for Myocardium in Percutaneous Coronary Intervention Related to Inflammation.

OBJECTIVES: Although injury of myocardium after percutaneous coronary intervention (PCI) has been reported, the mechanism and effect of exogenous phosphocreatine (PCr) supplementation on the injury are yet to be elucidated. Biomarkers, such as interleukin-6 (IL-6) and variations in white blood cells for inflammation, and serum cardiac troponin I (cTnI) for myocardial injury are examined. METHODS: A total of 105 patients undergoing PCI were included and randomly divided into two groups: control (treated with routine hydration therapy) and PCr (treated with additional intravenous infusion of exogenous PCr). The serum levels of biomarkers were detected at administration and 4, 12, 24, and 48 h after PCI, with natural logarithmic (loge) transformation of data when modeling assumptions were not fulfilled. RESULTS: The level of loge-transformed IL-6 increased in both groups, especially at 12 and 24 h after the operation, and that of PCr group was less than the control group at 48 h. The content of loge-transformed cTnI was significantly increased in both groups, while that of the PCr group was markedly lower than the control group at all time points after PCI. Moreover, the ratio of neutrophils was elevated at all time points after PCI, while that of the PCr group was lower at 48 h, and the variations in the ratio of lymphocytes showed opposite results. CONCLUSIONS: Exogenous phosphocreatine reduces stent implantation, triggers inflammation manifested as decreased serum levels of IL-6 and the aggregation of neutrophils, and protects the myocardium of the patients undergoing PCI. These findings provided the potential mechanism and treatment for myocardial injury associated with PCI.

SOHLH2 Suppresses Angiogenesis by Downregulating HIF1α Expression in Breast Cancer.

SOHLH2 has been demonstrated the downregulation in various cancers and the involvement in tumor growth and metastasis. However, the function of SOHLH2 on tumor angiogenesis and the underlying molecular mechanisms have not been interrogated. IHC staining results revealed that SOHLH2 was negatively associated with microvessel density (MVD), tumor size, histology grade, and metastasis. Overexpression of SOHLH2 inhibited the angiogenic behavior of human umbilical vein endothelial cells (HUVEC) by a tumor cell-mediated paracrine signal, while knockdown of SOHLH2 promoted HUVEC angiogenic behavior. Ectopic SOHLH2 expression remarkably suppressed tumor growth and MVD in xenograft tumors, downregulated the expression of hypoxia inducible factor-1 alpha (HIF1α)-mediated proangiogenic genes in vivo and in vitro, while knockdown of SOHLH2 had an opposite result. Furthermore, we found that upregulation of HIF1α reversed SOHLH2-induced suppression of breast cancer angiogenesis, while KC7F2, the inhibitor of HIF1α, could attenuate the promotion of angiogenesis by SOHLH2 silencing. Using Chromatin immunoprecipitation and luciferase reporter assays, we validated that SOHLH2 could directly bind to HIF1α promoter and repress its transcriptional activity. Collectively, SOHLH2 suppresses breast cancer angiogenesis by downregulating HIF1α transcription and may be a potential biomarker for anti-angiogenesis therapy. IMPLICATIONS: SOHLH2 directly represses HIF1α-mediated angiogenesis and serves as an important inhibitor of angiogenesis in breast cancer.

Analysis of center of mass acceleration and muscle activation in hemiplegic paralysis during quiet standing.

Hemiplegic paralysis after stroke may augment postural instability and decrease the balance control ability for standing. The center of mass acceleration (COMacc) is considered to be an effective indicator of postural stability for standing balance control. However, it is less studied how the COMacc could be affected by the muscle activities on lower-limbs in post-stroke hemiplegic patients. This study aimed to examine the effects of hemiplegic paralysis in post-stroke individuals on the amplitude and structural variabilities of COMacc and surface electromyography (sEMG) signals during quiet standing. Eleven post-stroke hemiplegic patients and the same number of gender- and age-matched healthy volunteers participated in the experiment. The sEMG signals of tibialis anterior (TA) and lateral gastrocnemius (LG) muscles of the both limbs, and the COMacc in the anterior-posterior direction with and without visual feedback (VF vs. NVF) were recorded simultaneously during quiet standing. The sEMG and COMacc were analyzed using root mean square (RMS) or standard deviation (SD), and a modified detrended fluctuation analysis based on empirical mode decomposition (EMD-DFA). Results showed that the SD and the scale exponent α of EMD-DFA of the COMacc from the patients were significantly higher than the values from the controls under both VF (p < 0.01) and NVF (p < 0.001) conditions. The RMSs of TA and LG on the non-paretic limbs were significantly higher than those on paretic limbs (p < 0.05) for both the patients and controls (p < 0.05). The TA of both the paretic and non-paretic limbs of the patients showed augmented α values than the TA of the controls (p < 0.05). The α of the TA and LG of non-paretic limbs, and the α of COMacc were significantly increased after removing visual feedback in patients (p < 0.05). These results suggested an increased amplitude variability but decreased structural variability of COMacc, associated with asymmetric muscle contraction between the paretic and the non-paretic limbs in hemiplegic paralysis, revealing a deficiency in integration of sensorimotor information and a loss of flexibility of postural control due to stroke.

Grape seed proanthocyanidins ameliorate diabetic nephropathy via modulation of levels of AGE, RAGE and CTGF.

BACKGROUND: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extracts (GSPE) are powerful antioxidants. However, the role of GSPE on advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE) and expression of connective tissue growth factor (CTGF) in DN has not been elucidated. Using streptozotocin-induced diabetic rats, we evaluated the effects of GSPE in DN. METHODS: Wistar rats were induced into diabetes using streptozotocin injections and diabetic rats were treated with GSPE (dosage: 500 mg x kg(-1) x day(-1)) for 24 weeks. The renal pathological changes were examined with PAS staining and electron microscope. The mRNA and protein expression of RAGE and CTGF in kidney were detected by RT-PCR, Western blot and immunohistochemical staining. RESULTS: Treated animals showed reduction in serum AGEs (p < 0.01), proteinuria (p < 0.01) and systolic blood pressure (p < 0.01). GSPE reduced the expression of RAGE (p < 0.01) and CTGF (p < 0.01) in the kidney, which were contributing to reversal of extracellular matrix accumulation in DN. CONCLUSION: Our results suggest that GSPE hold substantial promise for the treatment of DN. GSPE can decrease proteinuria, attenuating the progression of nephropathy in diabetic rats. Renoprotective effects of GSPE are correlated with suppression on AGEs/RAGE axis, downregulating expression of CTGF.