Amniotic membrane transplantation for infectious keratitis: a systematic review and meta-analysis

Infectious keratitis (IK) is the 5th leading cause of blindness globally. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though adjuvant treatment or surgeries are often required in refractory cases of IK. This systematic review aimed to examine the effectiveness and safety of adjuvant amniotic membrane transplantation (AMT) for treating IK. Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for relevant articles. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies and case series (n > 5), were included. Primary outcome measure was time to complete corneal healing and secondary outcome measures included corrected-distance-visual-acuity (CDVA), uncorrected-distance-visual-acuity (UDVA), corneal vascularization and adverse events. A total of twenty-eight studies (including four RCTs) with 861 eyes were included. When compared to standard antimicrobial treatment alone, adjuvant AMT resulted in shorter mean time to complete corneal healing (- 4.08 days; 95% CI - 6.27 to - 1.88; p < 0.001) and better UDVA (- 0.26 logMAR; - 0.50 to - 0.02; p = 0.04) at 1 month follow-up in moderate-to-severe bacterial and fungal keratitis, with no significant difference in the risk of adverse events (risk ratio 0.80; 0.46-1.38; p = 0.42). One RCT demonstrated that adjuvant AMT resulted in better CDVA and less corneal vascularization at 6 months follow-up (both p < 0.001). None of the RCTs examined the use of adjuvant AMT in herpetic or Acanthamoeba keratitis, though the benefit was supported by a number of case series. In conclusion, AMT serves as a useful adjuvant therapy in improving corneal healing and visual outcome in bacterial and fungal keratitis (low-quality evidence). Further adequately powered, high-quality RCTs are required to ascertain its therapeutic potential, particularly for herpetic and Acanthamoeba keratitis. Future standardization of the core outcome set in IK-related trials would be invaluable

Effectiveness of adjuvant photoactivated chromophore corneal collagen cross-linking versus standard antimicrobial treatment for infectious keratitis: a systematic review protocol

OBJECTIVE: The objective of this review is to systematically examine the effectiveness of adjuvant photoactivated chromophore for keratitis - corneal collagen cross-linking (PACK-CXL) versus standard antimicrobial treatment alone for corneal healing in patients with infectious keratitis. INTRODUCTION: Infectious keratitis is a major cause for corneal blindness globally. Broad-spectrum antimicrobial therapy is currently the standard treatment, but there is a growing need for alternative or adjuvant antimicrobial treatment, due to the emerging antimicrobial resistance, long treatment duration and cost of treatment. Photoactivated chromophore for keratitis - corneal collagen cross-linking has been increasingly used as an adjuvant treatment for infectious keratitis but high-quality evidence is limited. INCLUSION CRITERIA: This review will consider studies that include patients with infectious keratitis, encompassing bacterial, fungal, acanthamoeba, viral, mixed or culture-negative presumed infectious keratitis cases. Patients who have a previous history of infectious keratitis before the study or those that had less than seven days' follow-up from the start of the treatment will be excluded. METHODS: The electronic databases to be searched will include MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Only English articles will be included. Titles, abstracts and full text of the relevant studies will be assessed by two independent reviewers. The extracted data will include specific details about the study, including authors and study title, year of publication, sample size, populations, and study methods. A meta-analysis will be performed for the included randomized controlled trials when there are sufficient similarities in the reporting of outcome measures. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019131290

Effectiveness and safety of early adjuvant amniotic membrane transplant versus standard antimicrobial treatment for infectious keratitis: a systematic review protocol

OBJECTIVE: The objective of this review is to systematically examine the effectiveness of early adjuvant amniotic membrane transplant versus standard antimicrobial therapy for infectious keratitis. INTRODUCTION: Infectious keratitis is a major cause of corneal blindness worldwide. Broad-spectrum topical antimicrobial therapy is currently the gold standard for treatment. Amniotic membrane transplant has been employed as an adjuvant therapy to promote corneal healing; however, high-quality evidence is limited. INCLUSION CRITERIA: This review will consider studies that include patients of all ages with all types of infectious keratitis, including bacterial, fungal, viral, acanthamoeba, mixed, and culture-negative presumed infectious keratitis. The authors will exclude patients who have undergone other types of primary surgery other than amniotic membrane transplant during the initial management and those who had less than seven days' follow-up from the commencement of the treatment. METHODS: Electronic databases, including MEDLINE, Embase, Cochrane CENTRAL, and relevant registries, will be searched for pertinent studies. Titles, abstract, and full text of the relevant studies will be independently assessed by two reviewers. Extracted data will include authors, year of publication, sample size, types of amniotic membrane transplant techniques, types of causative microorganisms, main outcomes, visual acuity, and adverse events. No restriction will be applied to the date or language. Bibliographies of the included articles will be independently and manually screened by two authors to identify further relevant studies. Eligible studies will be critically appraised by two independent reviewers for methodological quality. A meta-analysis will be performed for the included randomized controlled trials when there are sufficient similarities. SYSTEMATIC REVIEW REGISTRATION NUMBER: This systematic review has been registered with PROSPERO (CRD42020175593)

One-step fabrication of biocompatible chitosan-coated ZnS and ZnS:Mn2+ quantum dots via a γ-radiation route

Biocompatible chitosan-coated ZnS quantum dots [CS-ZnS QDs] and chitosan-coated ZnS:Mn2+ quantum dots [CS-ZnS:Mn2+ QDs] were successfully fabricated via a convenient one-step γ-radiation route. The as-obtained QDs were around 5 nm in diameter with excellent water-solubility. These QDs emitting strong visible blue or orange light under UV excitation were successfully used as labels for PANC-1 cells. The cell experiments revealed that CS-ZnS and CS-ZnS:Mn2+ QDs showed low cytotoxicity and good biocompatibility, which offered possibilities for further biomedical applications. Moreover, this convenient synthesis strategy could be extended to fabricate other nanoparticles coated with chitosan

Critical international relations and the impact agenda

How should critical International Relations (IR) scholars approach the ‘impact agenda’? While most have been quite resistant to it, I argue in this essay that critical IR should instead embrace the challenge of impact – and that both IR as a field and the impact agenda more broadly would gain greatly from it doing so. I make this case through three steps. I show, firstly, that critical IR has till now been very much at the impact agenda’s margins, and that this situation contrasts strikingly with its well-established importance within IR teaching and research. I argue, secondly, that critical IR scholars both could and should do more impact work – that the current political conjuncture demands it, that many of the standard objections to doing so are misplaced, and indeed that ‘critical’ modes of research are in some regards better suited than ‘problem-solving’ ones to generating meaningful change – and offer a series of recommended principles for undertaking critically-oriented impact and engagement work. But I also argue, thirdly, that critical social science holds important lessons for the impact agenda, and that future impact assessments need to take these lessons on board – especially if critical IR scholarship is to embrace impact more fully. Critical IR, I submit, should embrace impact; but at the same time, research councils and assessments could do with modifying their approach to it, including by embracing a more critical and political understanding of what impact is and how it is achieved

Modified Alvarado Scoring System as a diagnostic tool for Acute Appendicitis at Bugando Medical Centre, Mwanza, Tanzania

<p>Abstract</p> <p>Background</p> <p>Decision-making in patients with acute appendicitis poses a diagnostic challenge worldwide, despite much advancement in abdominal surgery. The Modified Alvarado Scoring System (MASS) has been reported to be a cheap and quick diagnostic tool in patients with acute appendicitis. However, differences in diagnostic accuracy have been observed if the scores were applied to various populations and clinical settings. The purpose of this study was to evaluate the diagnostic value of Modified Alvarado Scoring System in patients with acute appendicitis in our setting.</p> <p>Methods</p> <p>A cross-sectional study involving all patients suspected to have acute appendicitis at Bugando Medical Centre over a six-month period between November 2008 and April 2009 was conducted. All patients who met the inclusion criteria were consecutively enrolled in the study. They were evaluated on admission using the MASS to determine whether they had acute appendicitis or not. All patients underwent appendicectomy according to the hospital protocol. The decision to operate was the prerogative of the surgeon or surgical resident based on overall clinical judgment and not the MASS. The diagnosis was confirmed by histopathological examination. Data was collected using a pre-tested coded questionnaire and analyzed using SPSS statistical computer software.</p> <p>Results</p> <p>A total number of 127 patients were studied. Their ages ranged from eight to 76 years (mean 29.64 ± 12.97). There were 37 (29.1%) males and 90 (70.9%) females (M: F = 1:2.4). All patients in this study underwent appendicectomy. The perforation rate was 9.4%. Histopathological examination confirmed appendicitis in 85 patients (66.9%) and the remaining 42 patients had normal appendix giving a negative appendicectomy rate of 33.1% (26.8% for males and 38.3% for females). The sensitivity and specificity of MASS in this study were 94.1% (males 95.8% and females 88.3%) and 90.4% (males 92.9% and females 89.7%) respectively. The Positive Predictive Value and Negative Predictive Value were 95.2% (males 95.5% and females 90.6%) and 88.4% (males 89.3% and females 80.1%) respectively. The accuracy of MASS was 92.9% (males 91.5% and females 87.6%).</p> <p>Conclusion</p> <p>The study shows that use of MASS in patients suspected to have acute appendicitis provides a high degree of diagnostic accuracy and can be employed at Bugando Medical Centre to improve the diagnostic accuracy of acute appendicitis and subsequently reduces negative appendicectomy and complication rates. However, additional investigations may be required to confirm the diagnosis in case of atypical presentation.</p

Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities

Background Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs. Methods To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay. Results Based on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO. Conclusion The modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO

Sequence Diversities of Serine-Aspartate Repeat Genes among Staphylococcus aureus Isolates from Different Hosts Presumably by Horizontal Gene Transfer

BACKGROUND: Horizontal gene transfer (HGT) is recognized as one of the major forces for bacterial genome evolution. Many clinically important bacteria may acquire virulence factors and antibiotic resistance through HGT. The comparative genomic analysis has become an important tool for identifying HGT in emerging pathogens. In this study, the Serine-Aspartate Repeat (Sdr) family has been compared among different sources of Staphylococcus aureus (S. aureus) to discover sequence diversities within their genomes. METHODOLOGY/PRINCIPAL FINDINGS: Four sdr genes were analyzed for 21 different S. aureus strains and 218 mastitis-associated S. aureus isolates from Canada. Comparative genomic analyses revealed that S. aureus strains from bovine mastitis (RF122 and mastitis isolates in this study), ovine mastitis (ED133), pig (ST398), chicken (ED98), and human methicillin-resistant S. aureus (MRSA) (TCH130, MRSA252, Mu3, Mu50, N315, 04-02981, JH1 and JH9) were highly associated with one another, presumably due to HGT. In addition, several types of insertion and deletion were found in sdr genes of many isolates. A new insertion sequence was found in mastitis isolates, which was presumably responsible for the HGT of sdrC gene among different strains. Moreover, the sdr genes could be used to type S. aureus. Regional difference of sdr genes distribution was also indicated among the tested S. aureus isolates. Finally, certain associations were found between sdr genes and subclinical or clinical mastitis isolates. CONCLUSIONS: Certain sdr gene sequences were shared in S. aureus strains and isolates from different species presumably due to HGT. Our results also suggest that the distributional assay of virulence factors should detect the full sequences or full functional regions of these factors. The traditional assay using short conserved regions may not be accurate or credible. These findings have important implications with regard to animal husbandry practices that may inadvertently enhance the contact of human and animal bacterial pathogens

Regeneration of Soft Tissues Is Promoted by MMP1 Treatment after Digit Amputation in Mice

The ratio of matrix metalloproteinases (MMPs) to the tissue inhibitors of metalloproteinases (TIMPs) in wounded tissues strictly control the protease activity of MMPs, and therefore regulate the progress of wound closure, tissue regeneration and scar formation. Some amphibians (i.e. axolotl/newt) demonstrate complete regeneration of missing or wounded digits and even limbs; MMPs play a critical role during amphibian regeneration. Conversely, mammalian wound healing re-establishes tissue integrity, but at the expense of scar tissue formation. The differences between amphibian regeneration and mammalian wound healing can be attributed to the greater ratio of MMPs to TIMPs in amphibian tissue. Previous studies have demonstrated the ability of MMP1 to effectively promote skeletal muscle regeneration by favoring extracellular matrix (ECM) remodeling to enhance cell proliferation and migration. In this study, MMP1 was administered to the digits amputated at the mid-second phalanx of adult mice to observe its effect on digit regeneration. Results indicated that the regeneration of soft tissue and the rate of wound closure were significantly improved by MMP1 administration, but the elongation of the skeletal tissue was insignificantly affected. During digit regeneration, more mutipotent progenitor cells, capillary vasculature and neuromuscular-related tissues were observed in MMP1 treated tissues; moreover, there was less fibrotic tissue formed in treated digits. In summary, MMP1 was found to be effective in promoting wound healing in amputated digits of adult mice. © 2013 Mu et al