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PubMed2026

A child and young person focused systematic review of scrotal ultrasound with Mitigants to identify missed torsion.

BACKGROUND: Diagnostic accuracy of ultrasound for adults is stated as excellent. Paediatric and adult acute scrotal diseases are different. Findings in adults may not apply in children. The authors have seen overconfidence and interpretation with adult disease in mind in children with scrotal pain and have seen testicular loss as a result. OBJECTIVES: To interrogate the literature methodologically to report diagnostic accuracy of ultrasound (US) for the acute scrotum specifically in CYP with a follow-up methodology which allows identification of missed torsion. STUDY DESIGN: We performed systematic review and meta-analysis of studies reporting true diagnostic accuracy of ultrasound for testicular torsion (TT). PubMed, MEDLINE, Scopus, and Web of Science databases were searched from platform start until September 2023 using MeSH terms with protocol as detailed on PROSPERO. Multiple author search was undertaken. Two authors extracted data for included studies. Study quality was reported through QUADAS-2 methodology. Surgical findings or 12 months follow up in non-operative cases would be the gold standard to identify late atrophy due to missed torsion. Studies with methodology to identify missed torsion outwith the initial consult were included for meta-analysis. RESULTS: A total of 6790 cases were reported from the 38 papers identified. Studies were often flawed with poor definition of outcomes and short follow-up duration. Meta-analysis of the 10 high-quality studies revealed pooled sensitivity and specificity of 0.93 and 0.99. Doppler US by trained individuals demonstrated excellent diagnostic accuracy. Nonetheless, on extrapolation of the data, especially where flow was preserved, 5.6% of torsions were missed. DISCUSSION/CONCLUSION: Our review confirms a high diagnostic accuracy of US for TT in CYP. However, a 5.6% missed torsion rate was found if flow alone was considered diagnostic. The authors suggest US should be used as an adjunct in ambiguous cases, ensuring that clinically obvious torsion goes to theatre immediately and is not delayed by ultrasound. TRIAL REGISTRATION: PROSPERO: CRD42023412619.

Humans↗
PubMed2006

Mitigation of age-dependent oxidative damage to DNA in rat heart by carnitine and lipoic acid.

Endogenous damage to mtDNA by free radicals is believed to be a major contributory factor to aging. Mitochondrial DNA exists in a highly genotoxic environment created by exposure to reactive oxygen species and thus are more vulnerable to free radical attack. In the present study we have focused on the age associated alterations to DNA during aging and in parallel investigated the efficacy of carnitine (300 mg/kg bw) and lipoic acid (100 mg/kg bw) for 28 days in altering these changes. We observed a decline in the content of both mitochondrial and nuclear DNA during aging with an exponential increase in the 8-OHdG levels. We also observed an age-dependent increase in DNA protein crosslinks and double strand and single strand breaks. Supplementation of carnitine and lipoic acid during aging process decreased the incidence of these DNA damage, therefore suggesting that this feeding regimen inhibits the accumulation of age-associated oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Ethanol-induced reduction of neurotrophin secretion in neonatal rat cerebellar granule cells is mitigated by vitamin E.

Ethanol exposure during nervous system development produces a range of abnormalities, and in humans may lead to the fetal alcohol syndrome. Among the mechanisms hypothesized to play roles in ethanol neurotoxicity are altered expression of supportive neurotrophic factors (NTFs), and cellular disturbances in oxidative processes. In this study, ethanol effects on secretion of two NTFs, brain-derived neurotrophic factor, and neurotrophin-3 were analyzed in neonatal rat cerebellar granule cells, and the potential of the antioxidant vitamin E to modulate ethanol effects was investigated. Ethanol exposure in these preparations reduced NTF secretion, but vitamin E appreciably ameliorated the ethanol effects. Possible mechanisms underlying both the ethanol effects on NTF secretion, and the protection of this antioxidant are considered.

Analysis of Variance↗
PubMed2004

Gene deletion of cystatin C aggravates brain damage following focal ischemia but mitigates the neuronal injury after global ischemia in the mouse.

Cystatin C is distributed in all human tissues and fluids with a particular abundance in the cerebrospinal fluid. Cystatin C is a strong endogenous inhibitor of lysosomal cysteine proteases, such as cathepsin B, L, H and S, that are involved in various biological processes such as degradation of cellular proteins and regulation of enzymes, as well as in pathological processes. Pharmacological inhibition of cathepsins has been shown to reduce neuronal damage after brain ischemia, suggesting that cystatin C is an endogenous neuroprotectant. Cystatin C has also amyloidogenic properties and is co-localized with beta-amyloid in degenerated neurons in Alzheimer's disease, suggesting a role in neuronal degeneration. To test the hypothesis that endogenous cystatin C is neuroprotective during brain ischemia, global and focal brain ischemia was induced in mice with the cystatin C gene knocked out. Following focal ischemia, larger brain infarcts were found in cystatin C knockout mice, probably due to a reduced inhibition of the cathepsins during ischemia. In contrast, brain damage after global ischemia was diminished in cystatin C knockout mice, suggesting that cystatin C has an aggravating effect on selective neuronal damage after global ischemia.

Animals↗
PubMed2005

All D-VIP mitigates vasodilation elicited by L-VIP, micellar L-VIP and micellar PACAP1-38, but not PACAP1-38, in vivo.

The purpose of this study was to determine whether all D-vasoactive intestinal peptide (VIP), an inactive optical isomer of L-VIP, modulates the vasorelaxant effects of human L-VIP and pituitary adenylate cyclase activating peptide (PACAP)1-38, two ubiquitous and pleiotropic neuropeptides that activate VPAC1 and VPAC2, two VIP subtype receptors, in the intact peripheral microcirculation. Using intravital microscopy, we found that suffusion of all D-VIP had no significant effects on arteriolar diameter in the intact hamster cheek pouch. However, all D-VIP significantly attenuated L-VIP-induced vasodilation in a concentration-dependent fashion (P<0.05). likewise, all D-VIP significantly attenuated the vasorelaxant effects of L-VIP associated with sterically stabilized phospholipid micelles (SSM; P<0.05). Although all D-VIP had no significant effects on L-PACAP1-38-induced vasodilation, it abrogated PACAP1-38 in SSM-induced responses (P<0.05). The effects of all D-VIP were specific because it had no significant effects on acetylcholine-, nitroglycerin- and bradykinin-induced vasodilation. Taken together, these data indicate that all D-VIP attenuates the vasorelaxant effects of random coil and alpha-helix L-VIP as well as those of alpha-helix but not random coil PACAP in the intact peripheral microcirculation in a specific fashion. These effects are mediated, most likely, through interactions with VPAC1/VPAC2 receptors. We suggest that all D-VIP could be exploited as a novel, safe and active targeting moiety of VPAC1/VPAC2 receptors in vivo.

Acetylcholine↗
PubMed2006

Matrix metalloproteinase-9 gene -1562C/T polymorphism mitigates preeclampsia.

Although the aetiology of preeclampsia is unknown, there is substantial evidence that it finds its roots in abnormal placentation. Prerequisites for successful placentation include trophoblast invasion, degradation and remodelling of the uterine decidual extracellular matrix, and apoptosis without thrombosis. We tested this hypothesis by analysing the effect of functional polymorphisms in the genes coding for MMP9, MMP3 and annexin A5 on the risk of preeclampsia using a case-control design. In 163 women with preeclampsia and 163 controls we studied the association with polymorphisms in the MMP9 (-1562 C/T), MMP3 (-1612 5A/6A) and annexin A5 (-1 C/T) genes using logistic regression analysis. A lower prevalence of the rare T allele of the MMP9 (-1562 C/T) polymorphism in women with preeclampsia was found (odds ratio 0.48, 95% confidence interval 0.25-0.90). The distribution of the MMP3 (-1612 5A/6A) and annexin A5 (-1 C/T) gene polymorphisms were similar in cases and controls. Our results suggest that the MMP9-1562T allele is associated with a reduced risk of preeclampsia and therefore may protect against maladaptation of the spiral arteries and decreased decidual degradation. The elevated MMP9 concentrations reported to be associated with the -1562T allele might be essential for the development of an adequate maternal-fetal interface early in pregnancy by facilitating trophoblast apoptosis and degradation.

Adult↗
PubMed2005

Mitigating the impact of multiple sclerosis on employment.

This article reviews the employment status of people with MS, the importance of employment, key barriers to employment, and compensatory and accommodation strategies to enhance employment. Resources and recommendations for health care providers to assist their patients in maintaining, securing, or leaving employment are presented.

Disability Evaluation↗
PubMed2004

Whole-catchment application of dolomite to mitigate episodic acidification of streams induced by sea-salt deposition.

To counteract mobilisation of potentially toxic aluminium (Al) ions to tributaries of salmon rivers, two paired-catchment experiments with terrestrial liming at two sites on the Norwegian west coast were performed. Streams at both sites experienced episodically elevated and potentially toxic Al levels induced by high deposition of sea salts. After application of 2 metric tons ha-1 of 0.2-2 mm dolomite powder at the Brommeland area, stream pH increased above critical levels at about pH=6.0 and remained stable throughout the monitoring period of 3.5 years. Inorganic aluminium decreased to below 20 microg Al L-1, a water quality supposed to be nontoxic for salmon. This was evident also during extreme weather conditions with large relative increases in chloride (Cl) concentrations and negative calculated nonmarine sodium (Na*) concentrations in the streams, indicating potentially toxic sea-salt effects. Cl changed from being closely related to increases in inorganic Al, especially at the Brommeland stream (R2=0.75), to being not important (R2=0.12), but still significant for its variation. At the Hovland area, receiving 1 ton ha-1 of 0-2 mm dolomite powder, stream pH and Al effects were less clear-cut, probably due to the lower dolomite dose. Stream concentrations of both NO3- and SO4(2-) increased significantly due to liming.

Aluminum Compounds↗
PubMed2005

Critical evaluation of measures to mitigate phosphorus losses from agricultural land to surface waters in Sweden.

The aim of this paper is to collate information on potential measures to reduce phosphorus (P) losses, with particular reference to Sweden. In Sweden, three dominant types of soils or soil profiles are at risk of suffering from high P losses through different pathways: clay soils with a naturally poor structure, usually situated on the large central plains, are prone to lose P through drain tiles; silty soils, usually situated on hilly terrain, are prone to erosion; and sandy soils with a low P sorption capacity in both topsoil and subsoil and that have had heavy applications of fertilisers, are prone to high leaching losses. Fields with such soils and landscape position with connectivity to surface waters may lose more than 0.5 kg P ha year-1 and often more than 1 kg P ha year-1. Losses of soluble reactive P (SRP) are commonly 30-50% of the total P losses. Improved soil tillage together with other measures aimed at improving soil structure are suggested to have the best potential to reduce losses, with short-term and long-term effects, for the clayey and silty soil profiles. For the silty soils, keeping the surface densely vegetated in winter and liming backfill of the drainage systems are suggested to be important ways to reduce the losses of particulate P (PartP). For sandy soils prone to P leaching, appropriate application of fertiliser and improved contact between fertiliser and the soil may be one of the few effective ways to reduce SRP losses.

Agriculture↗
PubMed2006

Dietary ascorbic acid and alpha-tocopherol mitigates oxidative stress induced by copper in the thornfish Terapon jarbua.

The protective effects of vitamins C and E against oxidative stress were evaluated in various tissues of thornfish Terapon jarbua exposed to copper. Preliminary bioassay tests performed with copper and T. jarbua revealed that 4.0, 2.5 and 1.0 mg L(-1) of copper were lethal (LC(100)), medial lethal (LC(50)) and sublethal (LC(0)) respectively. Oxidative stress parameters viz. lipid peroxidation, superoxide dismutase, catalase, glutathione peroxidase, and glutathione were evaluated in control and experimental fishes. Lipid peroxidation activity increased in tissues of copper exposed fishes, while the antioxidant system exhibited a reduction in their activity. On the contrary copper stressed fishes fed with vitamins C and E enriched pellet feed showed significant reduction in lipid peroxidation activity and the antioxidant levels increased reaching near normal levels comparable to control values. Bioaccumulation of copper was studied in addition to oxidative stress. Substantial copper residue was detected in the tissues of T. jarbua exposed to copper and the level of copper in tissues reduced when the fishes were treated with vitamins ensuring copper depuration and thereby protecting them against stress. We concluded that vitamin supplementation offered significant reduction of the oxidative stress mediated by copper and we discuss the possible application of vitamins in costal aquaculture process.

Animals↗
PubMed2025

TET2-mutant myeloid cells mitigate Alzheimer's disease progression via CNS infiltration and enhanced phagocytosis in mice.

Clonal hematopoiesis (CH) is associated with many age-related diseases, but its interaction with Alzheimer's disease (AD) remains unclear. Here, we show that TET2-mutant CH is associated with a 47% reduced risk of late-onset AD (LOAD) in the UK Biobank, whereas other drivers of CH do not confer protection. In a mouse model of AD, transplantation of Tet2-mutant bone marrow reduced cognitive decline and &#x3b2;-amyloid plaque formation, effects not observed with Dnmt3a-mutant marrow. Bone-marrow-derived microglia-like cells were detected at an increased rate in Tet2-mutant marrow recipients, and TET2-mutant human induced pluripotent stem cell (iPSC)-derived microglia were more phagocytic and hyperinflammatory than DNMT3A-mutant or wild-type microglia. Strikingly, single-cell RNA sequencing (scRNA-seq) revealed that macrophages and patrolling monocytes were increased in brains of mice transplanted with Tet2-mutant marrow in response to chemokine signaling. These studies reveal a TET2-specific protective effect of CH on AD pathogenesis mediated by peripheral myeloid cell infiltration.

Animals↗
PubMed2006

Vitamin E but not St. John's wort mitigates leukopenia caused by cancer chemotherapy in rats.

Dietary supplements are used by most patients with cancer. As nutraceuticals can interact with many drugs, this study investigated the effect of herbal remedies and vitamins on the toxicity of representative cancer chemotherapeutic agents. Fisher 344 rats were fed a standard cereal-based diet or the same diet with additional vitamin E in low (50 mg/kg) or high (750 mg/kg) concentrations, or with added St. John's wort (400 mg/kg). The LD50 was determined after the administration of chemotherapy drugs. Neither low or high vitamin E supplements nor St. John's wort significantly changed the LD50 for doxorubicin, docetaxel, or cyclophosphamide. The nadir white blood cell (WBC) count was significantly higher (P = 0.004) after docetaxel in rats supplemented with low-dose vitamin E, but the drop in WBC count from initial to nadir levels (Nfall) was greater in rats fed a diet containing high vitamin E supplementation (P = 0.04). Similarly, the Nfall was greater in the standard and high vitamin E dietary groups than in the low vitamin E group after cyclophosphamide (P = 0.03). No effect of vitamin E or St. John's wort supplementation occurred on doxorubicin pharmacokinetics. Neither vitamin E nor St. John's wort had an important effect on the mitochondrial deoxyribonucleic acid (DNA) damage caused by either doxorubicin or docetaxel. These data suggest that the leucopenia caused by some chemotherapeutic agents can be modified by dietary supplementation with vitamin E, but the effect seems to be dose-dependent. St. John's wort had neither a beneficial nor a detrimental effect on chemotherapy-induced toxicity.

Animals↗
PubMed2006

Static-charging mitigation and contamination avoidance by selective carbon coating of TEM samples.

Prior to transmission electron microscopy (TEM) analyses, insulating specimens need to become coated with a charge-draining layer. Rather than coating the entire TEM foil with a thin film of homogeneous thickness, selective coating is proposed. Using a novel preparation tool, peripheral parts of the sample are coated with a relatively thick (4-8 nm) carbon film while the central, electron-transparent part of the sample is hidden behind a shape-adopted mask and thus not directly exposed to carbon deposition. Beneath the mask, an ultrathin (3-7 A) carbon film is formed that is (i) thick enough to drain charges evolving upon electron irradiation in the electron microscope and (ii) thin enough to avoid typical contamination effects caused by superficial carbon diffusion. Consequently, image quality is becoming enhanced in high-resolution imaging and sensitivity is significantly increased in all nano-beam related techniques including elemental analytics, convergent-beam and nano-beam electron diffraction, and spectral imaging.

Journal Article↗
PubMed2004

Chemical characterisation of natural organic substrates for biological mitigation of acid mine drainage.

The current approach of the biological treatment of acid mine drainage by means of a passive remediation system involves the choice of an appropriate organic substrate as electron donor for sulphate reducers. Nowadays this selection is one of the critical steps in the performance of such treatment, as this depends to a great extent on the degradability of the organic substrate. Thus, a prior characterisation of the organic substrate predicting its biodegradability would be desirable before embarking on an extensive large-scale application. The aim of this study was to correlate the chemical composition (lignin content) of four different natural organic substrates (compost, sheep and poultry manures, oak leaf) and their capacity to sustain bacterial activity in an attempt to predict biodegradation from chemical characterisation. The results showed that the lower the content of lignin in the organic substrate, the higher its biodegradability and capacity for developing bacterial activity. Of the four organic materials, sheep and poultry manures and oak leaf evolved reducing conditions and sustained active sulphidogenesis, which coupled with the decrease in sulphate concentration indicated bacterial activity. Sheep manure was clearly the most successful organic material as electron donor (sulphate removal >99%), followed by poultry manure and oak leaf (sulphate removal of 80%). Compost appeared to be too poor in carbon to promote sulphate-reducing bacteria activity by itself. Column experiments emphasised the importance of considering the residence time as a key factor in the performance of continuous systems. With a residence time of 0.73 days, sheep manure did not promote sulphidogenesis. However, extending residence time to 2.4 and 9.0 days resulted in an increase in the sulphate removal to 18% and 27%, respectively.

Animals↗
PubMed2005

Characterization of hemodynamic events following intravascular infusion of recombinant adenovirus reveals possible solutions for mitigating cardiovascular responses.

Intravascular administration of recombinant adenovirus (rAd) in cancer patients has been well tolerated. However, dose-limiting hemodynamic responses associated with suppression of cardiac output have been observed at doses of 7.5 x 10(13) particles. While analysis of hemodynamic responses induced by small-molecule pharmaceuticals is well established, little is known about the cardiovascular effects of rAd. Telemetric cardiovascular (CV) monitoring in mice was utilized to measure hemodynamic events following intravascular rAd administration. Electrocardiogram analysis revealed a block in the SA node 3-4 min postinfusion, resulting in secondary pacemaking initiated at the AV node. This was associated with acute bradycardia, reduced blood pressure, and hypothermia followed by gradual recovery. Adenovirus-primed murine sera with high neutralizing antibody (nAb) titers could inhibit CV responses, whereas human sera with equivalent nAb titers induced by natural infection were, surprisingly, not inhibitory. Interestingly, repeat dosing within 2-4 h of the primary injection resulted in desensitization, resembling tachyphylaxis, for subsequent CV responses. Last, depletion of Kupffer cells prior to rAd infusion precluded induction of CV responses. These inhibitory effects suggest that rAd interactions with certain cells of the reticular endothelial system are associated with induction of CV responses. Significantly, these studies may provide insight into management of acute adverse effects following rAd systemic delivery, enabling a broadening of therapeutic index.

Adenoviridae↗