Nevin Manimala

Eur Surg Res. 2022 Apr 8. doi: 10.1159/000524431. Online ahead of print.

ABSTRACT

INTRODUCTION: Ultrasound (US) imaging enables tissue visualization in high spatial resolution with short examination times. Thus, it is often applied in preclinical research. Diagnostic US, including contrast-enhanced ultrasound (CEUS), are considered to be well tolerated by laboratory animals although no systematic study has been performed to confirm this claim. Therefore, the aim of this study was to screen for possible effects of US and CEUS examinations on welfare of healthy mice. Additionally, the potential influence of CEUS and molecular CEUS on well-being and therapy response to regorafenib was investigated in breast cancer-bearing mice.

MATERIAL AND METHODS: 40 healthy Balb/c mice were randomly assigned for examination with US or CEUS (3x/week) for four weeks. Untreated healthy mice and mice receiving only isoflurane anesthesia served as controls (n= 10/group). Ninety-four 4T1 tumor-bearing Balb/c mice were allocated randomly to the following groups: no imaging, isoflurane anesthesia, CEUS and molecular CEUS. They either received 10 mg/kg regorafenib or vehicle solution daily by oral gavage. Animals were examined three times within two weeks. CEUS measurements were performed using phospholipid-microbubbles and phospholipid-microbubbles targeting the vascular endothelial growth factor receptor-2 were applied for molecular CEUS. Welfare evaluation was performed by daily observational score sheets, measuring the heart rate, Rotarod performance and fecal corticosterone metabolites twice per week. On the last day, pathological changes of serum corticosterone concentrations, hemograms, and organ weights were obtained. Moreover, a potential influence of isoflurane anesthesia, CEUS and molecular CEUS on regorafenib response in tumor-bearing mice was examined. Analysis of variance and Dunnett post hoc test were performed as statistical analyses.

RESULTS: Severity parameters were not altered after repeated US and CEUS examinations of healthy mice, but spleen sizes were significantly lower after isoflurane anesthesia. In tumor-bearing mice, no effect on animal-welfare after repeated CEUS and molecular CEUS could be observed. However, leukocyte counts and spleen weights of tumor-bearing mice were significantly lower in animals examined with CEUS and molecular CEUS compared to the control groups. This effect was not visible in regorafenib-treated animals.

CONCLUSIONS: Repeated US and (molecular) CEUS have no detectable impact on animal welfare in healthy and tumor-bearing mice. However, CEUS and molecular CEUS in combination with isoflurane anesthesia might attenuate immunological processes in tumor-bearing animals and may consequently affect responses to anti-tumor therapy.

PMID:35398847 | DOI:10.1159/000524431

Caries Res. 2022 Apr 8. doi: 10.1159/000524458. Online ahead of print.

ABSTRACT

Visual attention is a significant gateway to a child’s mind, and looking is one of the first behaviours young children develop. Untreated caries and the resulting poor dental aesthetics can have adverse emotional and social impacts on children’s oral health-related quality of life due to its detrimental effects on self-esteem and self-concept. Therefore, we explored preschool children’s eye movement patterns and visual attention to images with and without dental caries via eye movement analysis using hidden Markov models (EMHMM). We calibrated a convenience sample of 157 preschool children to the eye-tracker (Tobii Nano Pro) to ensure standardisation. Consequently, each participant viewed the same standardised pictures with and without dental caries while an eye-tracking device tracked their eye movements. Subsequently, based on the sequence of viewed regions of interest (ROIs), a transition matrix was developed where the participants previously viewed ROI informed their subsequently considered ROI. Hence, an individual’s HMM was estimated from their eye movement data using a variational Bayesian approach to determine the optimal number of ROIs automatically. Consequently, this data-driven approach generated the visual task participants’ most representative eye movement patterns. Preschool children exhibited two different eye movement patterns, distributed (78%) and selective (21%), which was statistically significant. Children switched between images with more similar probabilities in the distributed pattern while children remained looking at the same ROI than switching to the other ROI in the selective pattern. Nevertheless, all children exhibited an equal starting fixation on the right or left image and noticed teeth. The study findings reveal that most preschool children did not have an attentional bias to images with and without dental caries. Furthermore, only a few children selectively fixated on images with dental caries. Therefore, selective eye-movement patterns may strongly predict preschool children’s sustained visual attention to dental caries. Nevertheless, future studies are essential to fully understand the developmental origins of differences in visual attention to common oral health presentations in children. Finally, EMHMM is appropriate for assessing inter-individual differences in children’s visual attention.

PMID:35398845 | DOI:10.1159/000524458

Water Res. 2022 Mar 25;217:118362. doi: 10.1016/j.watres.2022.118362. Online ahead of print.

ABSTRACT

Aquatic environments in industrial, and e-waste recycling areas might undergo severe contamination; however, there are few studies comprehensively assessing the pollution status of organophosphate esters (OPEs) in these two areas. Here, we applied both atmospheric pressure chemical ionization (APCI) and electron spray ionization (ESI) sources in our target, suspect, and functional group-dependent screening strategy, which enhanced the confidence for confirmation on precursor ions of OPEs. Then, n=53 sediment samples (30 from the industrial area, and 23 from the e-waste recycling area) were analyzed. Twenty-three out of 30 target OPEs were quantifiable in these analyzed samples. Total OPE concentrations (Σ₃₀OPEs) in samples from e-waste recycling area range from 12.8 to 9250 ng/g dry weight (dw), that are statistically significantly greater (t-test, p < 0.001) than those from industrial area (25.1-5520 ng/g dw). Σ₃₀OPEs in the sediments from industrial, or e-waste recycling area are statistically significantly greater (one-way ANOVA, p < 0.001) as compared to those (32.0-369 ng/g dw) from Taihu Lake in our previous study. In sediment from three areas, suspect and non-target analysis fully or tentatively identified other 20 OPEs. Four of them have not been recorded or registered in any of online chemical databases, and they are tentatively named as ((methoxy(phenoxy)phosphoryl)oxy)phenyl diphenyl phosphate (mPPODP), (tert-butyl)phenyl (ethyne-oxidane) bis(2,4-di-tert-butylphenyl) phosphate (TPBDTP), bis(dichlorophenyl) propane-1,3-diyl bis(hexylated phosphate) (BDCBHP), and bis(2-hexadecoxyethyl) ethyl phosphate (BHEPP). Overall, this study provided new insights regarding both analytical methodology and pollution status of OPEs, and highlights that elevated concentrations and high diversity of OPEs exist in sediments from industrial, and e-waste recycling areas.

PMID:35398804 | DOI:10.1016/j.watres.2022.118362

Sex Med. 2022 Apr 7;10(3):100509. doi: 10.1016/j.esxm.2022.100509. Online ahead of print.

ABSTRACT

BACKGROUND: Leptin, which was only discovered in humans in 1994, has recently been shown to have a possible link with premature ejaculation.

AIM: To evaluate whether serum leptin levels differed between patients with premature ejaculation and healthy men, and to analyze the changes in leptin levels before and after treatment.

METHODS: Six studies assessing the relationship between leptin and premature ejaculation published up to October 2021 were identified from multiple databases (PubMed, Web of Science, Cochrane) and the data were analyzed by Stata software.

OUTCOMES: Differences in leptin levels in premature ejaculation patients and healthy people, and changes of leptin levels in premature ejaculation population before and after treatment.

RESULTS: Analysis of studies assessing differences in leptin concentrations between patients with PE and healthy men showed that there was a statistically significant difference in leptin levels between PE patients and controls (WMD (95% CI) = 17.89 (8.64, 27.14), P < .001). On the other hand, the analysis of data from 3 studies describing serum leptin levels in PE patients before and after treatment with selective serotonin reuptake inhibitors (SSRIs) showed that there was a significant decrease with leptin levels in PE patients after treatment (WMD (95%CI) = 22.06 (17.21, 26.92), P < .001).

CLINICAL IMPLICATIONS: It is possible that leptin can be used as a new marker for premature ejaculation.

STRENGTH & LIMITATIONS: The strength of this study is that it is the first meta- analysis to assess the differences of serum leptin levels between patients with premature ejaculation and healthy subjects and the changes of leptin levels before and after treatment in patients with premature ejaculation. A major limitation is that a greater heterogeneity was identified through our analysis, however we did not find a definitive source of heterogeneity.

CONCLUSION: There was a statistically significant relationship between serum leptin levels and patients with PE. In addition, serum leptin levels in patients with PE decreased significantly after 8 weeks of treatment with SSRIs. Liu G, Zhang Y, Zhang W, et al. Novel Marker for Premature Ejaculation: Serum Leptin Level. Sex Med 2022;XX:XXXXXX.

PMID:35398789 | DOI:10.1016/j.esxm.2022.100509

EBioMedicine. 2022 Apr 7;79:103986. doi: 10.1016/j.ebiom.2022.103986. Online ahead of print.

ABSTRACT

BACKGROUND: SARS-CoV-2 Omicron variant evades immunity from past infection or vaccination and is associated with a greater risk of reinfection among recovered COVID-19 patients. We assessed the serum neutralizing antibody (NAb) activity against Omicron variant (Omicron NAb) among recovered COVID-19 patients with or without vaccination.

METHODS: In this prospective cohort study with 135 recovered COVID-19 patients, we determined the serum NAb titers against ancestral virus or variants using a live virus NAb assay. We used the receiver operating characteristic analysis to determine the optimal cutoff for a commercially-available surrogate NAb assay.

FINDINGS: Among recovered COVID-19 patients, the serum live virus geometric mean Omicron NAb titer was statistically significantly higher among BNT162b2 recipients compared to non-vaccinated individuals (85.4 vs 5.6,P < 0.0001). The Omicron seropositive rates in live virus NAb test (NAb titer ≥10) were statistically significantly higher among BNT162b2 (90.6% [29/32];P < 0.0001) or CoronaVac (36.7% [11/30]; P = 0.0115) recipients when compared with non-vaccinated individuals (12.3% [9/73]). Subgroup analysis of CoronaVac recipients showed that the Omicron seropositive rates were higher among individuals with two doses than those with one dose (85.7% vs 21.7%; P = 0.0045). For the surrogate NAb assay, a cutoff of 109.1 AU/ml, which is 7.3-fold higher than the manufacturer’s recommended cutoff, could achieve a sensitivity and specificity of 89.5% and 89.8%, respectively, in detecting Omicron NAb.

INTERPRETATION: Among individuals with prior COVID-19, one dose of BNT162b2 or two doses of CoronaVac could induce detectable serum Omicron NAb. Our result would be particularly important for guiding vaccine policies in countries with COVID-19 vaccine shortage.

FUNDING: Health and Medical Research Fund, Richard and Carol Yu, Michael Tong (see acknowledgments for full list).

PMID:35398786 | DOI:10.1016/j.ebiom.2022.103986

J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Mar 12;1197:123225. doi: 10.1016/j.jchromb.2022.123225. Online ahead of print.

ABSTRACT

Our previous studies showed that Shuangshen Pingfei Formula (SSPF) exhibited anti-fibrosis effect, but its biochemical changes at the metabolic level remain unclear. In this study, an integrative approach of gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS)-based non-targeted metabolomics and multivariate statistical analysis was employed to explore the metabolic changes of serum samples from different stages of bleomycin-induced pulmonary fibrosis (PF) rats (PFRs: M7, M14, M21 and M28) treated with SSPF extracts. Potential biomarkers for PF were screened. Benzenebutanoic acid, pyroglutamic acid, cholic acid, 1-monopalmitin, succinic acid and palmitoleic acid may be potential biomarkers of the early inflammation stage of PF (M7-M14). 3,4-dimethylbenzoic acid, glutamic acid, glycine, proline, serine, taurine, etc. may be potential biomarkers for the advanced pulmonary fibrosis stage (M21-M28) of PF. The disturbance was mainly related to the disorder of lipid, amino acid metabolism. After SSPF treatment, the disorder was regulated and 67 metabolites were restored to a certain extent. Serine, proline, glutamine, 4-guanidinobutyric acid, phosphatidylethanolamine, lecithin and 9,10-epoxyoctadecene acids may be useful as biomarkers of the anti-fibrosis effect of SSPF.

PMID:35397413 | DOI:10.1016/j.jchromb.2022.123225

Vet Parasitol. 2022 Mar 26;305:109700. doi: 10.1016/j.vetpar.2022.109700. Online ahead of print.

ABSTRACT

Leishmaniosis is a zoonotic disease with a very complex pathogenesis modulated by the interaction between the parasite, the vector and the host. Although the pathological characteristics have been extensively studied in the typically affected organs, some locations such as muscles and reproductive organs have been less studied. The objective of this study was to evaluate the presence of lesions in the temporal muscle and the male reproductive organs (testicle and epididymis) and correlate their characteristics with the presence of the parasite and with the clinical status of the dogs. The temporal muscle was studied in 25 infected beagle dogs (nine females and 16 males) and five uninfected control dogs (two females and three males) and the testicle and epididymis in the 19 males. Dogs were euthanized one year after infection and clinical signs, anti-Leishmania serum antibodies, and lymph node parasite load were assessed. Muscular and reproductive lesions were characterized by H&E and immunohistochemistry (IHC). The presence of the parasite in the lesions was evaluated using IHC and molecular techniques. Myositis was observed in 72% (18/25) of the dogs and was characterized by lymphoplasmacytic or histiocytic lesions. Mild and severe lesions were detected, the latter being statistically associated with the presence of the parasite and with the clinical status of the dogs. Orchitis was observed in 50% (8/16) of the dogs and was mainly mild and lymphoplasmacytic. No statistical relationship was found between testicular lesions and the presence of the parasite or the clinical status. Epididymitis was observed in 87.5% (14/16) of the dogs, and the lesions were often infiltrated by numerous histiocytes and neutrophils. Epididymal lesions were statistically associated with the clinical status of the dogs and with the presence of the parasite in the lesions. IgG and IgM immunoglobulins were found in all lesions, suggesting a local immune response with reactivation of the infection. Leishmania was more frequently detected in severe and histiocytic lesions, although some lesions had no detectable parasites. These results have shown that lesions in the temporal muscle, epididymis, and testicles are common in dogs infected by Leishmania infantum and that dogs may show a different response to infection. This response is characterized by varying degrees of cellular and immune responses associated with a variable presence of the parasite.

PMID:35397378 | DOI:10.1016/j.vetpar.2022.109700

Clin Neurol Neurosurg. 2022 Mar 26;216:107224. doi: 10.1016/j.clineuro.2022.107224. Online ahead of print.

ABSTRACT

BACKGROUND: Medical schools are responsible for training medical students to recognise and commence management for a broad spectrum of diseases, including clinical neuroscience conditions. To guide medical schools on topics that should be taught, speciality bodies have produced speciality-based core curricula. It is unknown to what extent these guidelines are used in designing each medical school’s curriculum. This survey aimed at assessing the use of these guidelines in designing clinical neuroscience curricula.

METHODS: This is a national survey. A 21-item questionnaire was sent to faculty members involved in the development of the clinical neuroscience curriculum in each medical school in the UK. Data collection occurred from1st September 2020-31 st August 2021. The Association of British Neurologists (ABN) and the Royal College of Surgeons England (RCSEng) guidelines were used as a benchmark. Descriptive statistics are reported.

RESULTS: Data was collected from 91.9% of eligible UK medical schools. 61.8% respondents were aware of ABN guidelines and 35.3% were aware of RCSEng guidelines. 17/28 (60.7%) topics recommended by the guidelines were taught in the neuroscience curricula of over 90% of the medical schools. Neurologists were involved in the design of the clinical neuroscience curriculum in 94.1% (n = 32/34) of medical schools, and neurosurgeons in 61.8%. Tutorials/seminars were used by all medical schools to teach clinical neuroscience content. Neurologists were involved in teaching at all schools and neurosurgeons in 70.6%. Objective Structured Clinical Examination (OSCE)/oral examinations and single best answer (SBA)/multiple-choice question (MCQ) tests were used in all medical schools as methods of assessment.

CONCLUSIONS: There is variation between medical schools on what clinical neuroscience topics are taught and by whom. Multi-modality educational delivery was evident. Some medical schools did not currently use, advertise, or recommend external clinical neuroscience educational resources; but there was support for future use of external resources including guidelines.

PMID:35397346 | DOI:10.1016/j.clineuro.2022.107224

Comput Biol Med. 2022 Apr 2;145:105435. doi: 10.1016/j.compbiomed.2022.105435. Online ahead of print.

ABSTRACT

Systemic lupus erythematosus is a chronic autoimmune disease that affects the kidney in most patients. Lupus nephritis (LN) is divided into six categories by the International Society of Nephrology/Renal Pathology Society (ISN/RPS). The purpose of this research is to build a framework for discriminating between ISN/RPS pure class V(MLN) and classes III ± V or IV ± V (PLN) using real clinical data. The framework is developed by merging a hybrid stochastic optimizer, moth-flame algorithm (HMFO), with a support vector machine (SVM), dubbed HMFO-SVM. The HMFO is constructed by enhancing the original moth-flame algorithm (MFO) with a bee-foraging learning operator, which guarantees that the algorithm speeds convergence and departs from the local optimum. The HMFO is used to optimize parameters and select features simultaneously for SVM on clinical SLE data. On 23 benchmark tests, the suggested HMFO method is validated. Finally, clinical data from LN patients are analyzed to determine the efficacy of HMFO-SVM over other SVM rivals. The statistical findings indicate that all measures have predictive capabilities and that the suggested HMFO-SVM is more stable for analyzing systemic LN. HMFO-SVM may be used to analyze LN as a feasible computer-assisted technique.

PMID:35397339 | DOI:10.1016/j.compbiomed.2022.105435

Complement Ther Clin Pract. 2022 Apr 4;48:101580. doi: 10.1016/j.ctcp.2022.101580. Online ahead of print.

ABSTRACT

BACKGROUND: The best physiotherapeutic approach in shoulder pathology that generates prolonged immobilization is still uncertain. Kinesitherapy remains the most widely used option. Myofascial therapy is a therapeutic approach in which the aim is to release fascial tension and regain mobility although its efficacy in shoulder pathology has not been sufficiently studied. This Prospective, single-blind randomized controlled trial in a university hospital setting aimed to compare the efficacy of myofascial therapy and kinesitherapy in improving function in shoulder pathology with prolonged immobilization.

METHODS: Patients were randomly assigned to a control group or to the intervention group.Both groups completed a therapeutic exercise program.

MAIN OUTCOME MEASURES: The QuickDash questionnaire was the primary outcome, Pain Visual Analog Scale and the Range Of Motion of the shoulder were the secondary outcomes. The outcomes were evaluated at baseline (T0), at 4 (T2), 8 (T2), and 12 weeks (T3) RESULTS: 44 participants were included. In the analysis of evolution over time, a significant improvement in functionality and range of motion measurements was observed in both groups (p < 0.05), although at 12 weeks only Myofasical Group achieved a clinically and statistically significant reduction in pain. Comparative analysis at 12 weeks revealed no statistically significant differences between the two therapies in the variables explored.

CONCLUSIONS: Both, myofascial therapy and kinesitherapy can improve function, mobility, and pain in patients with painful shoulder associated with prolonged immobilization, with no significant differences between therapies, although in the medium term only myofascial therapy achieves a clinically and statistically significant improvement in pain.

TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov NCT04944446.

PMID:35397306 | DOI:10.1016/j.ctcp.2022.101580