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Human Reproduction Update Nov 2022To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones...
BACKGROUND
To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field.
OBJECTIVE AND RATIONALE
This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman's syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases.
OUTCOMES
Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather than by meta-analysis. Hydrogels and scaffolds were commonly applied in various bioengineering-related studies of the female reproductive tract. Emerging technologies, such as organoids and bioprinting, offered personalized diagnoses and alternative treatment options, respectively. Promising microfluidic systems combining various bioengineering approaches have also shown translational value.
WIDER IMPLICATIONS
The complexity of the molecular, endocrine and tissue-level interactions regulating female reproduction present challenges for bioengineering approaches to replace female reproductive organs. However, interdisciplinary work is providing valuable insight into the physicochemical properties necessary for reproductive biological processes to occur. Defining the landscape of reproductive bioengineering technologies currently available and under development for women can provide alternative models for toxicology/drug testing, ex vivo fertility options, clinical therapies and a basis for future organ regeneration studies.
Topics: Animals; Female; Humans; Pregnancy; Bioengineering; Embryo Implantation; Genitalia, Female; Reproduction; Uterus
PubMed: 35652272
DOI: 10.1093/humupd/dmac025 -
Frontiers in Psychology 2017Nonsuicidal self-injury (NSSI) refers to the intentional self-inflicted destruction of body tissue without suicidal intention and for purposes not socially sanctioned....
Nonsuicidal self-injury (NSSI) refers to the intentional self-inflicted destruction of body tissue without suicidal intention and for purposes not socially sanctioned. Our paper presents an up-to-date overview on nonsuicidal, self-injurious behaviors. In accordance with PRISMA guidelines, a systematic literature search was conducted across two databases, PubMed and PsycARTICLES, regarding the main features of NSSI with a focus on epidemiological and etiologic data, diagnostic criteria, and functions. All English articles, published between 1998 and 2016, were considered, and screened against a priori inclusion/exclusion criteria. The search terms include: self-harm, self-injury, NSSI, epidemiology, comorbidity, gender, functions and DSM. We also examined the references of the retrieved articles. NSSI is most common among adolescents and young adults, and the age of onset is reported to occur between 12 and 14 years. Comorbidity with borderline personality disorder (BPD) and eating disorders is often reported. DSM-5 includes NSSI as a condition requiring further study. This review gives an overview of the prevalence rates (7.5-46.5% adolescents, 38.9% university students, 4-23% adults) and main causes that appear to stem from childhood trauma, comorbidity with many other disorders and several functions of NSSI, and the potential independence of a NSSI disorder. Over the years, interest in NSSI grew to such an extent that an ongoing debate was instigated on whether NSSI should be considered as a diagnosis in its own right and given its own category. This paper provides an up-to-date overview on self-injury, what is known about it and what remains to be done. Clearly, our understanding of the main issues of NSSI has increased in last two decades. However, future researches is needed to examine the developmental trajectories, cultural backgrounds and shed light on the risk factors and functions as well as clarify its role as an independent diagnostic entity.
PubMed: 29167651
DOI: 10.3389/fpsyg.2017.01946 -
PloS One 2017The bench press exercise (BP) plays an important role in recreational and professional training, in which muscle activity is an important multifactorial phenomenon. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The bench press exercise (BP) plays an important role in recreational and professional training, in which muscle activity is an important multifactorial phenomenon. The objective of this paper is to systematically review electromyography (EMG) studies performed on the barbell BP exercise to answer the following research questions: Which muscles show the greatest activity during the flat BP? Which changes in muscle activity are related to specific conditions under which the BP movement is performed?
STRATEGY
PubMed, Scopus, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library were searched through June 10, 2016. A combination of the following search terms was used: bench press, chest press, board press, test, measure, assessment, dynamometer, kinematics and biomechanics. Only original, full-text articles were considered.
RESULTS
The search process resulted in 14 relevant studies that were included in the discussion. The triceps brachii (TB) and pectoralis major (PM) muscles were found to have similar activity during the BP, which was significantly higher than the activity of the anterior deltoid. During the BP movement, muscle activity changes with exercise intensity, velocity of movement, fatigue, mental focus, movement phase and stability conditions, such as bar vibration or unstable surfaces. Under these circumstances, TB is the most common object of activity change.
CONCLUSIONS
PM and TB EMG activity is more dominant and shows greater EMG amplitude than anterior deltoid during the BP. There are six factors that can influence muscle activity during the BP; however, the most important factor is exercise intensity, which interacts with all other factors. The research on muscle activity in the BP has several unresolved areas, such as clearly and strongly defined guidelines to perform EMG measurements (e.g., how to elaborate with surface EMG limits) or guidelines for the use of exact muscle models.
Topics: Electromyography; Exercise; Humans; Muscle Contraction; Muscle, Skeletal; Psychomotor Performance
PubMed: 28170449
DOI: 10.1371/journal.pone.0171632 -
Redox Report : Communications in Free... Dec 2018p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative... (Review)
Review
BACKGROUND
p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis.
METHODS
A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases. Articles published in the English language between January 1, 1990 and March 1, 2017 were identified and isolated based on the analysis of p53 in skeletal muscle in both animal and cell culture models.
RESULTS
Literature was categorized according to the modality of imposed oxidative stress including exercise, diet modification, exogenous oxidizing agents, tissue manipulation, irradiation, and hypoxia. With low to moderate levels of oxidative stress, p53 is involved in activating pathways that increase time for cell repair, such as cell cycle arrest and autophagy, to enhance cell survival. However, with greater levels of stress intensity and duration, such as with irradiation, hypoxia, and oxidizing agents, the role of p53 switches to facilitate increased cellular stress levels by initiating DNA fragmentation to induce apoptosis, thereby preventing aberrant cell proliferation.
CONCLUSION
Current evidence confirms that p53 acts as a threshold regulator of cellular homeostasis. Therefore, within each modality, the intensity and duration are parameters of the oxidative stressor that must be analyzed to determine the role p53 plays in regulating signaling pathways to maintain cellular health and function in skeletal muscle.
ABBREVIATIONS
Acadl: acyl-CoA dehydrogenase, long chain; Acadm: acyl-CoA dehydrogenase, C-4 to C-12 straight chain; AIF: apoptosis-inducing factor; Akt: protein kinase B (PKB); AMPK: AMP-activated protein kinase; ATF-4: activating transcription factor 4; ATM: ATM serine/threonine kinase; Bax: BCL2 associated X, apoptosis regulator; Bcl-2: B cell Leukemia/Lymphoma 2 apoptosis regulator; Bhlhe40: basic helix-loop-helix family member e40; BH3: Borane; Bim: bcl-2 interacting mediator of cell death; Bok: Bcl-2 related ovarian killer; COX-IV: cytochrome c oxidase IV; cGMP: Cyclic guanosine monophosphate; c-myc: proto-oncogene protein; Cpt1b: carnitine palmitoyltransferase 1B; Dr5: death receptor 5; eNOS: endothelial nitric oxide synthase; ERK: extracellular regulated MAP kinase; Fas: Fas Cell surface death receptor; FDXR: Ferredoxin Reductase; FOXO3a: forkhead box O3; Gadd45a: growth arrest and DNA damage-inducible 45 alpha; GLS2: glutaminase 2; GLUT 1 and 4: glucose transporter 1(endothelial) and 4 (skeletal muscle); GSH: Glutathione; Hes1: hes family bHLH transcription factor 1; Hey1: hes related family bHLH transcription factor with YRPW motif 1; HIFI-α: hypoxia-inducible factor 1, α-subunit; HK2: Hexokinase 2; HSP70: Heat Shock Protein 70; HO: Hydrogen Peroxide; Id2: inhibitor of DNA-binding 2; IGF-1-BP3: Insulin-like growth factor binding protein 3; IL-1β: Interleukin 1 beta; iNOS: inducible nitric oxide synthase; IRS-1: Insulin receptor substrate 1; JNK: c-Jun N-terminal kinases; LY-83583: 6-anilino-5,8-quinolinedione; inhibitor of soluble guanylate cyclase and of cGMP production; Mdm 2/ 4: Mouse double minute 2 homolog (mouse) Mdm4 (humans); mtDNA: mitochondrial DNA; MURF1: Muscle RING-finger protein-1; MyoD: Myogenic differentiation 1; MyoG: myogenin; Nanog: Nanog homeobox; NF-kB: Nuclear factor-κB; NO: nitric oxide; NoxA: phorbol-12-myristate-13-acetate-induced protein 1 (Pmaip1); NRF-1: nuclear respiratory factor 1; Nrf2: Nuclear factor erythroid 2-related factor 2; P21: Cdkn1a cyclin-dependent kinase inhibitor 1A (P21); P38 MAPK: mitogen-activated protein kinases; p53R2: p53 inducible ribonucleotide reductase gene; P66Shc: src homology 2 domain-containing transforming protein C1; PERP: p53 apoptosis effector related to PMP-22; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PGM: phosphoglucomutase; PI3K: Phosphatidylinositol-4,5-bisphosphate 3-kinase; PKCβ: protein kinase c beta; PTEN: phosphatase and tensin homolog; PTIO: 2-phenyl-4, 4, 5, 5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) has been used as a nitric oxide (NO) scavenger; Puma: The p53 upregulated modulator of apoptosis; PW1: paternally expressed 3 (Peg3); RNS: Reactive nitrogen species; SIRT1: sirtuin 1; SCO2: cytochrome c oxidase assembly protein; SOD2: superoxide dismutase 2; Tfam: transcription factor A mitochondrial; TIGAR: Trp53 induced glycolysis repulatory phosphatase; TNF-a: tumor necrosis factor a; TRAF2: TNF receptor associated factor 2; TRAIL: type II transmembrane protein.
Topics: Animals; Diet; Exercise; Humans; Muscle, Skeletal; Oxidative Stress; Oxygen; Proto-Oncogene Mas; Radiation Injuries; Tumor Suppressor Protein p53
PubMed: 29298131
DOI: 10.1080/13510002.2017.1416773 -
The Cochrane Database of Systematic... Aug 2018Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a million people were newly diagnosed with rifampicin-resistant TB in 2016. Xpert MTB/RIF (Xpert) is a World Health Organization (WHO)-recommended, rapid, automated, nucleic acid amplification assay that is used widely for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum specimens. This Cochrane Review assessed the accuracy of Xpert in extrapulmonary specimens.
OBJECTIVES
To determine the diagnostic accuracy of Xpert a) for extrapulmonary TB by site of disease in people presumed to have extrapulmonary TB; and b) for rifampicin resistance in people presumed to have extrapulmonary TB.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature (LILACS), Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number (ISRCTN) Registry, and ProQuest up to 7 August 2017 without language restriction.
SELECTION CRITERIA
We included diagnostic accuracy studies of Xpert in people presumed to have extrapulmonary TB. We included TB meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, and disseminated TB. We used culture as the reference standard. For pleural TB, we also included a composite reference standard, which defined a positive result as the presence of granulomatous inflammation or a positive culture result. For rifampicin resistance, we used culture-based drug susceptibility testing or MTBDRplus as the reference standard.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, assessed risk of bias and applicability using the QUADAS-2 tool. We determined pooled predicted sensitivity and specificity for TB, grouped by type of extrapulmonary specimen, and for rifampicin resistance. For TB detection, we used a bivariate random-effects model. Recognizing that use of culture may lead to misclassification of cases of extrapulmonary TB as 'not TB' owing to the paucibacillary nature of the disease, we adjusted accuracy estimates by applying a latent class meta-analysis model. For rifampicin resistance detection, we performed univariate meta-analyses for sensitivity and specificity separately to include studies in which no rifampicin resistance was detected. We used theoretical populations with an assumed prevalence to provide illustrative numbers of patients with false positive and false negative results.
MAIN RESULTS
We included 66 unique studies that evaluated 16,213 specimens for detection of extrapulmonary TB and rifampicin resistance. We identified only one study that evaluated the newest test version, Xpert MTB/RIF Ultra (Ultra), for TB meningitis. Fifty studies (76%) took place in low- or middle-income countries. Risk of bias was low for patient selection, index test, and flow and timing domains and was high or unclear for the reference standard domain (most of these studies decontaminated sterile specimens before culture inoculation). Regarding applicability, in the patient selection domain, we scored high or unclear concern for most studies because either patients were evaluated exclusively as inpatients at tertiary care centres, or we were not sure about the clinical settings.Pooled Xpert sensitivity (defined by culture) varied across different types of specimens (31% in pleural tissue to 97% in bone or joint fluid); Xpert sensitivity was > 80% in urine and bone or joint fluid and tissue. Pooled Xpert specificity (defined by culture) varied less than sensitivity (82% in bone or joint tissue to 99% in pleural fluid and urine). Xpert specificity was ≥ 98% in cerebrospinal fluid, pleural fluid, urine, and peritoneal fluid.Xpert testing in cerebrospinal fluidXpert pooled sensitivity and specificity (95% credible interval (CrI)) against culture were 71.1% (60.9% to 80.4%) and 98.0% (97.0% to 98.8%), respectively (29 studies, 3774 specimens; moderate-certainty evidence).For a population of 1000 people where 100 have TB meningitis on culture, 89 would be Xpert-positive: of these, 18 (20%) would not have TB (false-positives); and 911 would be Xpert-negative: of these, 29 (3%) would have TB (false-negatives).For TB meningitis, ultra sensitivity and specificity against culture (95% confidence interval (CI)) were 90% (55% to 100%) and 90% (83% to 95%), respectively (one study, 129 participants).Xpert testing in pleural fluidXpert pooled sensitivity and specificity (95% CrI) against culture were 50.9% (39.7% to 62.8%) and 99.2% (98.2% to 99.7%), respectively (27 studies, 4006 specimens; low-certainty evidence).For a population of 1000 people where 150 have pleural TB on culture, 83 would be Xpert-positive: of these, seven (8%) would not have TB (false-positives); and 917 would be Xpert-negative: of these, 74 (8%) would have TB (false-negatives).Xpert testing in urineXpert pooled sensitivity and specificity (95% CrI) against culture were 82.7% (69.6% to 91.1%) and 98.7% (94.8% to 99.7%), respectively (13 studies, 1199 specimens; moderate-certainty evidence).For a population of 1000 people where 70 have genitourinary TB on culture, 70 would be Xpert-positive: of these, 12 (17%) would not have TB (false-positives); and 930 would be Xpert-negative: of these, 12 (1%) would have TB (false-negatives).Xpert testing for rifampicin resistanceXpert pooled sensitivity (20 studies, 148 specimens) and specificity (39 studies, 1088 specimens) were 95.0% (89.7% to 97.9%) and 98.7% (97.8% to 99.4%), respectively (high-certainty evidence).For a population of 1000 people where 120 have rifampicin-resistant TB, 125 would be positive for rifampicin-resistant TB: of these, 11 (9%) would not have rifampicin resistance (false-positives); and 875 would be negative for rifampicin-resistant TB: of these, 6 (1%) would have rifampicin resistance (false-negatives).For lymph node TB, the accuracy of culture, the reference standard used, presented a greater concern for bias than in other forms of extrapulmonary TB.
AUTHORS' CONCLUSIONS
In people presumed to have extrapulmonary TB, Xpert may be helpful in confirming the diagnosis. Xpert sensitivity varies across different extrapulmonary specimens, while for most specimens, specificity is high, the test rarely yielding a positive result for people without TB (defined by culture). Xpert is accurate for detection of rifampicin resistance. For people with presumed TB meningitis, treatment should be based on clinical judgement, and not withheld solely on an Xpert result, as is common practice when culture results are negative.
Topics: Antibiotics, Antitubercular; Bacterial Proteins; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; False Negative Reactions; False Positive Reactions; Humans; Mycobacterium tuberculosis; Reagent Kits, Diagnostic; Reference Standards; Rifampin; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Meningeal
PubMed: 30148542
DOI: 10.1002/14651858.CD012768.pub2 -
Frontiers in Immunology 2020With the epidemic of human obesity, dietary fats have increasingly become a focal point of biomedical research. Epidemiological studies indicate that high-fat diets...
With the epidemic of human obesity, dietary fats have increasingly become a focal point of biomedical research. Epidemiological studies indicate that high-fat diets (HFDs), especially those rich in long-chain saturated fatty acids (e.g., Western Diet, National Health Examination survey; NHANES 'What We Eat in America' report) have multi-organ pro-inflammatory effects. Experimental studies have confirmed some of these disease associations, and have begun to elaborate mechanisms of disease induction. However, many of the observed effects from epidemiological studies appear to be an over-simplification of the mechanistic complexity that depends on dynamic interactions between the host, the particular fatty acid, and the rather personalized genetics and variability of the gut microbiota. Of interest, experimental studies have shown that certain saturated fats (e.g., lauric and myristic fatty acid-rich coconut oil) could exert the opposite effect; that is, desirable anti-inflammatory and protective mechanisms promoting gut health by unanticipated pathways. Owing to the experimental advantages of laboratory animals for the study of mechanisms under well-controlled dietary settings, we focus this review on the current understanding of how dietary fatty acids impact intestinal biology. We center this discussion on studies from mice and rats, with validation in cell culture systems or human studies. We provide a scoping overview of the most studied diseases mechanisms associated with the induction or prevention of Inflammatory Bowel Disease in rodent models relevant to Crohn's Disease and Ulcerative Colitis after feeding either high-fat diet (HFD) or feed containing specific fatty acid or other target dietary molecule. Finally, we provide a general outlook on areas that have been largely or scarcely studied, and assess the effects of HFDs on acute and chronic forms of intestinal inflammation.
Topics: Adipokines; Animals; Colitis, Ulcerative; Crohn Disease; Cytokines; Fatty Acids; Gastrointestinal Microbiome; Humans; Inflammation Mediators; Intestinal Absorption; Intestinal Mucosa; Oxidative Stress; Signal Transduction; T-Lymphocytes
PubMed: 33603741
DOI: 10.3389/fimmu.2020.604989 -
The Cochrane Database of Systematic... Feb 2021Bacterial folliculitis and boils are globally prevalent bacterial infections involving inflammation of the hair follicle and the perifollicular tissue. Some... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bacterial folliculitis and boils are globally prevalent bacterial infections involving inflammation of the hair follicle and the perifollicular tissue. Some folliculitis may resolve spontaneously, but others may progress to boils without treatment. Boils, also known as furuncles, involve adjacent tissue and may progress to cellulitis or lymphadenitis. A systematic review of the best evidence on the available treatments was needed.
OBJECTIVES
To assess the effects of interventions (such as topical antibiotics, topical antiseptic agents, systemic antibiotics, phototherapy, and incision and drainage) for people with bacterial folliculitis and boils.
SEARCH METHODS
We searched the following databases up to June 2020: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five trials registers up to June 2020. We checked the reference lists of included studies and relevant reviews for further relevant trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed systemic antibiotics; topical antibiotics; topical antiseptics, such as topical benzoyl peroxide; phototherapy; and surgical interventions in participants with bacterial folliculitis or boils. Eligible comparators were active intervention, placebo, or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were 'clinical cure' and 'severe adverse events leading to withdrawal of treatment'; secondary outcomes were 'quality of life', 'recurrence of folliculitis or boil following completion of treatment', and 'minor adverse events not leading to withdrawal of treatment'. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included 18 RCTs (1300 participants). The studies included more males (332) than females (221), although not all studies reported these data. Seventeen trials were conducted in hospitals, and one was conducted in clinics. The participants included both children and adults (0 to 99 years). The studies did not describe severity in detail; of the 232 participants with folliculitis, 36% were chronic. At least 61% of participants had furuncles or boils, of which at least 47% were incised. Duration of oral and topical treatments ranged from 3 days to 6 weeks, with duration of follow-up ranging from 3 days to 6 months. The study sites included Asia, Europe, and America. Only three trials reported funding, with two funded by industry. Ten studies were at high risk of 'performance bias', five at high risk of 'reporting bias', and three at high risk of 'detection bias'. We did not identify any RCTs comparing topical antibiotics against topical antiseptics, topical antibiotics against systemic antibiotics, or phototherapy against sham light. Eleven trials compared different oral antibiotics. We are uncertain as to whether cefadroxil compared to flucloxacillin (17/21 versus 18/20, risk ratio (RR) 0.90, 95% confidence interval (CI) 0.70 to 1.16; 41 participants; 1 study; 10 days of treatment) or azithromycin compared to cefaclor (8/15 versus 10/16, RR 1.01, 95% CI 0.72 to 1.40; 31 participants; 2 studies; 7 days of treatment) differed in clinical cure (both very low-certainty evidence). There may be little to no difference in clinical cure rate between cefdinir and cefalexin after 17 to 24 days (25/32 versus 32/42, RR 1.00, 95% CI 0.73 to 1.38; 74 participants; 1 study; low-certainty evidence), and there probably is little to no difference in clinical cure rate between cefditoren pivoxil and cefaclor after 7 days (24/46 versus 21/47, RR 1.17, 95% CI 0.77 to 1.78; 93 participants; 1 study; moderate-certainty evidence). For risk of severe adverse events leading to treatment withdrawal, there may be little to no difference between cefdinir versus cefalexin after 17 to 24 days (1/191 versus 1/200, RR 1.05, 95% CI 0.07 to 16.62; 391 participants; 1 study; low-certainty evidence). There may be an increased risk with cefadroxil compared with flucloxacillin after 10 days (6/327 versus 2/324, RR 2.97, 95% CI 0.60 to 14.62; 651 participants; 1 study; low-certainty evidence) and cefditoren pivoxil compared with cefaclor after 7 days (2/77 versus 0/73, RR 4.74, 95% CI 0.23 to 97.17; 150 participants; 1 study; low-certainty evidence). However, for these three comparisons the 95% CI is very wide and includes the possibility of both increased and reduced risk of events. We are uncertain whether azithromycin affects the risk of severe adverse events leading to withdrawal of treatment compared to cefaclor (274 participants; 2 studies; very low-certainty evidence) as no events occurred in either group after seven days. For risk of minor adverse events, there is probably little to no difference between the following comparisons: cefadroxil versus flucloxacillin after 10 days (91/327 versus 116/324, RR 0.78, 95% CI 0.62 to 0.98; 651 participants; 1 study; moderate-certainty evidence) or cefditoren pivoxil versus cefaclor after 7 days (8/77 versus 5/73, RR 1.52, 95% CI 0.52 to 4.42; 150 participants; 1 study; moderate-certainty evidence). We are uncertain of the effect of azithromycin versus cefaclor after seven days due to very low-certainty evidence (7/148 versus 4/126, RR 1.26, 95% CI 0.38 to 4.17; 274 participants; 2 studies). The study comparing cefdinir versus cefalexin did not report data for total minor adverse events, but both groups experienced diarrhoea, nausea, and vaginal mycosis during 17 to 24 days of treatment. Additional adverse events reported in the other included studies were vomiting, rashes, and gastrointestinal symptoms such as stomach ache, with some events leading to study withdrawal. Three included studies assessed recurrence following completion of treatment, none of which evaluated our key comparisons, and no studies assessed quality of life.
AUTHORS' CONCLUSIONS
We found no RCTs regarding the efficacy and safety of topical antibiotics versus antiseptics, topical versus systemic antibiotics, or phototherapy versus sham light for treating bacterial folliculitis or boils. Comparative trials have not identified important differences in efficacy or safety outcomes between different oral antibiotics for treating bacterial folliculitis or boils. Most of the included studies assessed participants with skin and soft tissue infection which included many disease types, whilst others focused specifically on folliculitis or boils. Antibiotic sensitivity data for causative organisms were often not reported. Future trials should incorporate culture and sensitivity information and consider comparing topical antibiotic with antiseptic, and topical versus systemic antibiotics or phototherapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents, Local; Bias; Carbuncle; Child; Child, Preschool; Female; Furunculosis; Humans; Infant; Infant, Newborn; Male; Middle Aged; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33634465
DOI: 10.1002/14651858.CD013099.pub2 -
The Cochrane Database of Systematic... Sep 2022Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert... (Review)
Review
BACKGROUND
Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of tuberculosis in children and adolescents.
OBJECTIVES
To assess the diagnostic accuracy of Xpert Ultra for detecting: pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance, in children with presumed tuberculosis. Secondary objectives To investigate potential sources of heterogeneity in accuracy estimates. For detection of tuberculosis, we considered age, comorbidity (HIV, severe pneumonia, and severe malnutrition), and specimen type as potential sources. To summarize the frequency of Xpert Ultra trace results.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, three other databases, and three trial registers without language restrictions to 9 March 2021.
SELECTION CRITERIA
Cross-sectional and cohort studies and randomized trials that evaluated Xpert Ultra in HIV-positive and HIV-negative children under 15 years of age. We included ongoing studies that helped us address the review objectives. We included studies evaluating sputum, gastric, stool, or nasopharyngeal specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), and fine needle aspirate or surgical biopsy tissue (lymph node tuberculosis). For detecting tuberculosis, reference standards were microbiological (culture) or composite reference standard; for stool, we also included Xpert Ultra performed on a routine respiratory specimen. For detecting rifampicin resistance, reference standards were drug susceptibility testing or MTBDRplus.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and, using QUADAS-2, assessed methodological quality judging risk of bias separately for each target condition and reference standard. For each target condition, we used the bivariate model to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We summarized the frequency of Xpert Ultra trace results; trace represents detection of a very low quantity of Mycobacterium tuberculosis DNA. We assessed certainty of evidence using GRADE.
MAIN RESULTS
We identified 14 studies (11 new studies since the previous review). For detection of pulmonary tuberculosis, 335 data sets (25,937 participants) were available for analysis. We did not identify any studies that evaluated Xpert Ultra accuracy for tuberculous meningitis or lymph node tuberculosis. Three studies evaluated Xpert Ultra for detection of rifampicin resistance. Ten studies (71%) took place in countries with a high tuberculosis burden based on WHO classification. Overall, risk of bias was low. Detection of pulmonary tuberculosis Sputum, 5 studies Xpert Ultra summary sensitivity verified by culture was 75.3% (95% CI 64.3 to 83.8; 127 participants; high-certainty evidence), and specificity was 97.1% (95% CI 94.7 to 98.5; 1054 participants; high-certainty evidence). Gastric aspirate, 7 studies Xpert Ultra summary sensitivity verified by culture was 70.4% (95% CI 53.9 to 82.9; 120 participants; moderate-certainty evidence), and specificity was 94.1% (95% CI 84.8 to 97.8; 870 participants; moderate-certainty evidence). Stool, 6 studies Xpert Ultra summary sensitivity verified by culture was 56.1% (95% CI 39.1 to 71.7; 200 participants; moderate-certainty evidence), and specificity was 98.0% (95% CI 93.3 to 99.4; 1232 participants; high certainty-evidence). Nasopharyngeal aspirate, 4 studies Xpert Ultra summary sensitivity verified by culture was 43.7% (95% CI 26.7 to 62.2; 46 participants; very low-certainty evidence), and specificity was 97.5% (95% CI 93.6 to 99.0; 489 participants; high-certainty evidence). Xpert Ultra sensitivity was lower against a composite than a culture reference standard for all specimen types other than nasopharyngeal aspirate, while specificity was similar against both reference standards. Interpretation of results In theory, for a population of 1000 children: • where 100 have pulmonary tuberculosis in sputum (by culture): - 101 would be Xpert Ultra-positive, and of these, 26 (26%) would not have pulmonary tuberculosis (false positive); and - 899 would be Xpert Ultra-negative, and of these, 25 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in gastric aspirate (by culture): - 123 would be Xpert Ultra-positive, and of these, 53 (43%) would not have pulmonary tuberculosis (false positive); and - 877 would be Xpert Ultra-negative, and of these, 30 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in stool (by culture): - 74 would be Xpert Ultra-positive, and of these, 18 (24%) would not have pulmonary tuberculosis (false positive); and - 926 would be Xpert Ultra-negative, and of these, 44 (5%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in nasopharyngeal aspirate (by culture): - 66 would be Xpert Ultra-positive, and of these, 22 (33%) would not have pulmonary tuberculosis (false positive); and - 934 would be Xpert Ultra-negative, and of these, 56 (6%) would have tuberculosis (false negative). Detection of rifampicin resistance Xpert Ultra sensitivity was 100% (3 studies, 3 participants; very low-certainty evidence), and specificity range was 97% to 100% (3 studies, 128 participants; low-certainty evidence). Trace results Xpert Ultra trace results, regarded as positive in children by WHO standards, were common. Xpert Ultra specificity remained high in children, despite the frequency of trace results.
AUTHORS' CONCLUSIONS
We found Xpert Ultra sensitivity to vary by specimen type, with sputum having the highest sensitivity, followed by gastric aspirate and stool. Nasopharyngeal aspirate had the lowest sensitivity. Xpert Ultra specificity was high against both microbiological and composite reference standards. However, the evidence base is still limited, and findings may be imprecise and vary by study setting. Although we found Xpert Ultra accurate for detection of rifampicin resistance, results were based on a very small number of studies that included only three children with rifampicin resistance. Therefore, findings should be interpreted with caution. Our findings provide support for the use of Xpert Ultra as an initial rapid molecular diagnostic in children being evaluated for tuberculosis.
Topics: Adolescent; Antibiotics, Antitubercular; Child; Cross-Sectional Studies; HIV Infections; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Sensitivity and Specificity; Sputum; Tuberculosis, Lymph Node; Tuberculosis, Meningeal; Tuberculosis, Pulmonary
PubMed: 36065889
DOI: 10.1002/14651858.CD013359.pub3 -
Stem Cell Research & Therapy Apr 2023The first human brain organoid protocol was presented in the beginning of the previous decade, and since then, the field witnessed the development of many new brain...
BACKGROUND
The first human brain organoid protocol was presented in the beginning of the previous decade, and since then, the field witnessed the development of many new brain region-specific models, and subsequent protocol adaptations and modifications. The vast amount of data available on brain organoid technology may be overwhelming for scientists new to the field and consequently decrease its accessibility. Here, we aimed at providing a practical guide for new researchers in the field by systematically reviewing human brain organoid publications.
METHODS
Articles published between 2010 and 2020 were selected and categorised for brain organoid applications. Those describing neurodevelopmental studies or protocols for novel organoid models were further analysed for culture duration of the brain organoids, protocol comparisons of key aspects of organoid generation, and performed functional characterisation assays. We then summarised the approaches taken for different models and analysed the application of small molecules and growth factors used to achieve organoid regionalisation. Finally, we analysed articles for organoid cell type compositions, the reported time points per cell type, and for immunofluorescence markers used to characterise different cell types.
RESULTS
Calcium imaging and patch clamp analysis were the most frequently used neuronal activity assays in brain organoids. Neural activity was shown in all analysed models, yet network activity was age, model, and assay dependent. Induction of dorsal forebrain organoids was primarily achieved through combined (dual) SMAD and Wnt signalling inhibition. Ventral forebrain organoid induction was performed with dual SMAD and Wnt signalling inhibition, together with additional activation of the Shh pathway. Cerebral organoids and dorsal forebrain model presented the most cell types between days 35 and 60. At 84 days, dorsal forebrain organoids contain astrocytes and potentially oligodendrocytes. Immunofluorescence analysis showed cell type-specific application of non-exclusive markers for multiple cell types.
CONCLUSIONS
We provide an easily accessible overview of human brain organoid cultures, which may help those working with brain organoids to define their choice of model, culture time, functional assay, differentiation, and characterisation strategies.
Topics: Humans; Brain; Organoids; Prosencephalon; Induced Pluripotent Stem Cells; Neurons; Cell Differentiation
PubMed: 37061699
DOI: 10.1186/s13287-023-03302-x -
Journal of Bone and Joint Infection 2022: this systematic review aims to evaluate the concordance between preoperative synovial fluid culture and intraoperative tissue cultures in patients with periprosthetic... (Review)
Review
: this systematic review aims to evaluate the concordance between preoperative synovial fluid culture and intraoperative tissue cultures in patients with periprosthetic joint infection (PJI) undergoing total hip (THA) or knee arthroplasty (TKA) revision surgery. : this review was conducted in accordance with the preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) statement. Cochrane, Embase, PubMed, and Web of Science databases were searched to identify studies involving patients who had THA or TKA revision surgery for PJI and for whom preoperative synovial fluid culture and intraoperative tissue cultures were performed. Studies were only included if the diagnosis of PJI was based on the EBJIS (the European Bone and Joint Infection Society) or MSIS (Musculoskeletal Infection Society) criteria. Risk of bias was assessed using an amended version of Joanna Briggs Institute's (JBI) critical appraisal checklist for case series. : seven studies were included in this review comprising 1677 patients. All studies had a retrospective study design and five studies explored patients undergoing revision surgery of THA or TKA. Concordance rates varied between 52 % and 79 %, but different authors defined and calculated concordance differently. Six studies were judged as having an unclear to high risk of bias and one study as having a low risk of bias. : the included studies showed a wide range of concordance rates between preoperative synovial fluid culture and intraoperative tissue cultures and the majority of studies had a high risk of bias. Higher-quality studies are warranted to obtain a more accurate estimate of this concordance rate. We recommend continuing the use of a system such as the EBJIS definition or MSIS criteria when diagnosing PJI.
PubMed: 36644592
DOI: 10.5194/jbji-7-259-2022