Nevin Manimala

Respir Res. 2022 Sep 17;23(1):249. doi: 10.1186/s12931-022-02172-w.

ABSTRACT

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease caused by the induction of inflammatory cytokines and chemokines in the lungs. There is a dearth of drug applications that can be used to prevent cytokine storms in ARDS treatment. This study was designed to investigate the effects of tocilizumab and dexamethasone on oxidative stress, antioxidant parameters, and cytokine storms in acute lung injury caused by oleic acid in rats.

METHODS: Adult male rats were divided into five groups: the CN (healthy rats, n = 6), OA (oleic acid administration, n = 6), OA + TCZ-2 (oleic acid and tocilizumab at 2 mg/kg, n = 6), OA + TCZ-4 (oleic acid and tocilizumab at 4 mg/kg, n = 6), and OA + DEX-10 (oleic acid and dexamethasone at 10 mg/kg, n = 6) groups. All animals were euthanized after treatment for histopathological, immunohistochemical, biochemical, PCR, and SEM analyses.

RESULTS: Expressions of TNF-α, IL-1β, IL-6, and IL-8 cytokines in rats with acute lung injury induced by oleic acid were downregulated in the TCZ and DEX groups compared to the OA group (P < 0.05). The MDA level in lung tissues was statistically lower in the OA + TCZ-4 group compared to the OA group. It was further determined that SOD, GSH, and CAT levels were decreased in the OA group and increased in the TCZ and DEX groups (P < 0.05). Histopathological findings such as thickening of the alveoli, hyperemia, and peribronchial cell infiltration were found to be similar when lung tissues of the TCZ and DEX groups were compared to the control group. With SEM imaging of the lung tissues, it was found that the alveolar lining layer had become indistinct in the OA, OA + TCZ-2, and OA + TCZ-4 groups.

CONCLUSIONS: In this model of acute lung injury caused by oleic acid, tocilizumab and dexamethasone were effective in preventing cytokine storms by downregulating the expression of proinflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-8. Against the downregulation of antioxidant parameters such as SOD and GSH in the lung tissues caused by oleic acid, tocilizumab and dexamethasone upregulated them and showed protective effects against cell damage.

PMID:36115998 | DOI:10.1186/s12931-022-02172-w

BMC Musculoskelet Disord. 2022 Sep 17;23(1):870. doi: 10.1186/s12891-022-05817-5.

ABSTRACT

BACKGROUND: The difference between MRI (Magnetic resonance imaging)-R2* and T2 mapping sequences regarding their superiority in the detection of microstructural cartilage changes in knees with limited ROM (range of motion) was unknown.

METHODS: Twenty male cynomolgus monkeys (mean age: 10.65 ± 0.97 years) underwent knee ROM evaluations and were divided into three groups: Group A (n = 10), with similar left and right knee ROM; Group B (n = 5), with left knee ROM superior to right; and Group C (n = 5), with left knee ROM inferior to right. Twenty-eight ROIs (regions of interest) in the cartilage of the lateral (L) and medial (M) femoral trochlea (FT), anterior (A)/central (C)/posterior (P) femoral condyle (FC) and tibial plateau (TP) of both knees were identified in each monkey. The corresponding ROI values in R2* and T2 mapping sequences were recorded for analysis. One-way ANOVA, Chi-square tests and Pearson’s correlation analysis were used for statistical analyses.

RESULTS: Among the total 1120 ROIs, significant differences in R2* values among the three groups existed in two ROIs: cartilage of the right MPTP (F = 5.216, P = 0.017) and left MAFC (F = 4.919, P = 0.021). However, the T2 mapping values of all ROIs were similar among the three groups. Microstructural cartilage changes occurred more frequently in the medial (40 ROIs) than in the lateral (0 ROIs) knee compartment (χ² = 43.077, P < 0.001). The Group B cartilage R2* value of the right MPTP increased with the difference in bilateral knee ROM (r = 0.913, P = 0.030).

CONCLUSIONS: In knees with limited ROM, MRI-R2* sequence is superior to T2 mapping in the detection of microstructural cartilage changes, which the medial knee compartment was more susceptible to. Cartilage R2* values tend to increase with the amount of knee ROM loss.

PMID:36115988 | DOI:10.1186/s12891-022-05817-5

BMC Pediatr. 2022 Sep 17;22(1):552. doi: 10.1186/s12887-022-03603-9.

ABSTRACT

BACKGROUND: To explore the prevalence, outcome and perinatal risks of neonatal hypoxemic respiratory failure (NRF) in a survey of all livebirths from a regional network of perinatal-neonatal care during the transition period after 5-year universal health insurance implemented in China.

METHODS: Clinical data of all neonatal respiratory morbidities in Huai’an were retrospectively collected in the regional perinatal network database of all livebirths as vital statistics in 2015. NRF was defined as hypoxemia requiring continuous positive airway pressure (CPAP) and/or mechanical ventilation (MV) for at least 24 h. Mortality risks of antenatal and perinatal morbidities, major respiratory therapies and complications were analyzed by multivariable logistic regression model.

RESULTS: There were 788 NRF cases identified in 9.9% (7960) hospitalized, or 13.3‰ (59056) livebirths, in which 6.7% received intensive care and 93.0% critical care. The major underlying morbidities were respiratory distress syndrome (RDS, 36.4%) and pneumonia/sepsis (35.3%), treated mainly by CPAP, MV and surfactant. Significantly improved outcomes by surfactant in RDS were in patients with birthweight (BW) < 1500 g or gestational age (GA) < 32 weeks. The overall mortality rate in NRF was 18.4% whereas for those of BW < 1000 g and GA < 28 weeks, 70% and 54%, respectively. The multivariable regression analysis showed the highest odds for NRF death among meconium aspiration syndrome, congenital anomalies, BW < 1500 g and necrotizing enterocolitis, whereas born in level III hospitals, cesarean delivery, CPAP and MV were associated with markedly reduced death odds.

CONCLUSIONS: The salient findings with associated risk estimates reflected efficiency of respiratory support as critical care in a prefectural regional network infrastructure for annual livebirths in 5.6 million inhabitants. It implicated the representativeness of contemporaneous perinatal-neonatal care standard at medium to medium-high level, in one/fourth of the population of China, aiming at saving more life of very critical and preterm infants for better survival.

PMID:36115974 | DOI:10.1186/s12887-022-03603-9

BMC Cancer. 2022 Sep 17;22(1):988. doi: 10.1186/s12885-022-10085-6.

ABSTRACT

BACKGROUND: Anthracycline-induced cardiotoxicity is an irreversible cardiac cell injury. Therefore, it’s very important to identify influencing factors of anthracycline-induced subclinical cardiotoxicity (AISC). This study was designed to analyze the influencing factors of AISC in patients with diffuse large B-cell lymphoma (DLBCL) treated with the (R)-CHOP chemotherapy regimen.

METHODS: This is an ongoing observational prospective clinical trial. All patients underwent conventional echocardiography and speckle tracking echocardiography at the time of enrollment and during treatment. Changes of global longitudinal peak systolic strain were assessed after 3 cycles of (R)-CHOP chemotherapy, and patients were divided into the AISC and No-AISC groups. Demographic data, clinical variables, and biochemical variables were measured. Regression models, receiver operating characteristic curve analysis, and difference values were used to explore the relationships between variables and AISC.

RESULTS: Among 70 patients who completed 3 cycles of (R)-CHOP chemotherapy, 26 developed AISC. In multiple logistic regression, HDL-C (P = 0.047), ApoA1 (P = 0.022), TG (P = 0.029) and e’ (P = 0.008) were associated with AISC. The combination of HDL-C and NT-proBNP had the highest area under curves (AUC) for the diagnosis of AISC than HDL-C and NT-proBNP alone (AUC = 0.752, 95%CI: 0.63-0.87, P = 0.001). Between the No-AISC and AISC groups, there was no significant difference in HDL-C, ApoA1, and e’ at baseline and after 3 cycles of chemotherapy, respectively. The dynamic changes of HDL-C, ApoA1, and e’ from baseline to the end of the 3^rd cycle of chemotherapy showed statistically significant differences.

CONCLUSIONS: HDL-C, ApoA1, TG, and e’ are independent predictive factors in DLBCL cases treated with the (R)-CHOP chemotherapy regimen. The combination of HDL-C and NT-proBNP may improve the predictive ability for AISC in patients with DLBCL administered 3 cycles of (R)-CHOP chemotherapy. Dynamic changes of HDL-C, ApoA1, and e’ may be meaningful for predicting AISC.

TRIAL REGISTRATION: Our study was registered in the Chinese Clinical Trial Registry (Approval ID. ChiCTR2100054721 http://www.chictr.org.cn/showproj.aspx?proj=145082 ).

PMID:36115970 | DOI:10.1186/s12885-022-10085-6

BMC Gastroenterol. 2022 Sep 17;22(1):424. doi: 10.1186/s12876-022-02497-2.

ABSTRACT

BACKGROUND: Colonoscopy is a standard procedure for evaluating colon diseases and screening for colorectal cancer, and bowel cleanliness prior to colonoscopy is key. The aim of this study was to compare the bowel cleansing efficacy of low-volume (2 L) split-dose polyethylene glycol (PEG) plus single-dose (24 µg) lubiprostone (LB) and high-volume (4 L) split-dose PEG.

METHODS: Patients scheduled to undergo outpatient colonoscopy between December 2019 and June 2021 at Rajavithi Hospital were enrolled and randomized into two groups: 2 L PEG + LB or 4 L PEG. Colon cleanliness was evaluated using the Boston Bowel Preparation Scale (BBPS) by reviewing images of the colon after completion of colonoscopy. Secondary outcomes comprised cecal intubation rate, procedure time, withdrawal time, polyp detection rate, adenoma detection rate, patient satisfaction, compliance (based on complete ingestion of bowel preparation regimen), willingness to repeat the preparation regimen, and associated adverse events.

RESULTS: One hundred and forty patients were included, with 70 in each group. The mean total and segment-specific BBPS scores were not significantly different between groups. However, the rate of adequate bowel preparation was significantly higher in the 2 L PEG + LB group than the 4 L PEG group (100% [95% CI 94.6-100] versus 88.4% [95% CI 78.4-94.9], p = 0.004) in the per-protocol analysis. Colonic polyps were the most common finding. The polyp detection rate, adenoma detection rate, and all secondary outcomes were statistically similar in the two groups (p > 0.05).

CONCLUSIONS: The combination of 2 L split-dose PEG plus LB improves bowel cleanliness (based on BBPS scores) to a comparable degree to the standard 4 L split-dose PEG, without additional adverse events and with a lower PEG volume.

PMID:36115968 | DOI:10.1186/s12876-022-02497-2

BMC Ophthalmol. 2022 Sep 18;22(1):370. doi: 10.1186/s12886-022-02594-6.

ABSTRACT

OBJECTIVE: To analyze the changes in the prevalence of myopia and its relation to ocular biological parameters, and behaviors among primary school students in China, and understand the prevention and control of myopia.

METHODS: Cross-sectional surveys were performed on 7-9-year-old children in the yrs. 2012 and 2019. In addition, spherical equivalent refraction (SER), axial length (AL), and AL/corneal radius ratio (AL/CR ratio) were collected without cycloplegia. Participants completed detailed questionnaires on behavior related to myopia.

RESULTS: Data was collected on 623 children (8.02 ± 0.57 years old) in 2012 and 536 students in 2019 (8.09 ± 0.65 years old). The prevalence of myopia was 37.7% in 2012 and 39.9% in 2019. The SER was -0.25 (0.92) D in 2012 and -0.25 (1.25) in 2019. There was no statistical difference in the prevalence of myopia and SER over the 7 years (all P > 0.05). In 2019, the prevalence of myopia among girls demonstrated an increasing trend (33.8% vs. 37.8%), but there was no statistical difference (P > 0.05). The mean AL and AL/CR ratio of boys were decreasing (all P < 0.05). The proportion of children reading more than 2 h and using digital devices for more than 2 h per day after their classes in the 2019 group both decreased (all P < 0.05). However, the proportion of activities performed outdoors for more than 2 h./day decreased significantly (P = 0.001).

CONCLUSION: Compared with 2012, the prevalence of myopia in primary school students in 2019 was under control, which may be related to the improvement of children’s near-work behavior, but there was the problem of insufficient outdoor activity time. In terms of ocular biological parameters, the risk of myopia for boys in 2019 was lower.

PMID:36115954 | DOI:10.1186/s12886-022-02594-6

BMC Cancer. 2022 Sep 17;22(1):990. doi: 10.1186/s12885-022-10014-7.

ABSTRACT

BACKGROUND: A group of genetically altered cells that have not transformed into a clinical or histologically identifiable state of malignancy but contains a higher risk of transforming into one is known as the field of cancerization. Numerous molecules are being investigated for their significance in the development of this phenomenon. One such protein of this family is Kaiso also known as ZBTB33 (Zinc Finger and BTB Domain containing 33). This protein belongs to the POZ-ZF family of transcription factors and may have functional tasks similar to its other siblings such as the growth and development of vertebrates and the pathogenesis of neoplastic diseases. Nevertheless, its role in the pathogenesis, progression, epithelial mesenchyal transition and field cancerization in case of oral cancer still needs exploration. Hence, this study was designed to explore the expressional differences between the mucosa of controls and those diagnosed with oral squamous cell carcinoma (OSCC).

METHODS: Soft tissue samples were obtained from the main tumor, tumor periphery and opposite buccal mucosa of 50 oral cancer patients, whereas normal mucosa was taken from 50 volunteers undergoing elective tooth removal. The acquired samples were subjected to Immunohistochemical exploration for expression of Kaiso and E-Cadherin. The expression was measured using Image-J IHC profiler and summed as Optical density. The Optical density values were then subjected to statistical analysis.

RESULTS: Results revealed a significant differential expression of Kaiso between the mucosal tissues taken from oral cancer patients and controls (p-value: < 0.0001), showing almost 50% down-regulation of Kaiso in all three tissue samples taken from oral cancer patients as compared to normal mucosa.

CONCLUSION: Kaiso has a significant difference of expression in the mucosa of oral cancer patients as compared to the mucosa of normal patients, making it a probable contributor to disease pathogenesis and field cancerization.

PMID:36115941 | DOI:10.1186/s12885-022-10014-7

Mod Pathol. 2022 Sep 17. doi: 10.1038/s41379-022-01145-0. Online ahead of print.

ABSTRACT

Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Although histology and pathologic stage are important prognostic factors, better prognostic biomarkers are needed. The ribosomal protein S6 is a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway involved in protein synthesis and cell proliferation. In previous studies, low phosphorylated S6 (pS6) immunoreactivity was significantly correlated with longer progression-free survival (PFS) and overall survival (OS) in PM patients. We aimed to correlate pS6 expression to clinical data in a large multi-centre PM cohort as part of the European Thoracic Oncology Platform (ETOP) Mesoscape project. Tissue Micro Arrays (TMAs) of PM were constructed and expression of pS6 was evaluated by a semi-quantitatively aggregate H-score. Expression results were correlated to patient characteristics as well as OS/PFS. pS6 IHC results of 364 patients from 9 centres, diagnosed between 1999 and 2017 were available. The primary histology of included tumours was epithelioid (70.3%), followed by biphasic (24.2%) and sarcomatoid (5.5%). TMAs included both treatment-naïve and tumour tissue taken after induction chemotherapy. High pS6 expression (181 patients with H-score>1.41) was significantly associated with less complete resection. In the overall cohort, OS/PFS were not significantly different between pS6-low and pS6-high patients. In a subgroup analysis non-epithelioid (biphasic and sarcomatoid) patients with high pS6 expression showed a significantly shorter OS (p < 0.001, 10.7 versus 16.9 months) and PFS (p < 0.001, 6.2 versus 10.8 months). In subgroup analysis, in non-epithelioid PM patients high pS6 expression was associated with significantly shorter OS and PFS. These exploratory findings suggest a clinically relevant PI3K pathway activation in non-epithelioid PM which might lay the foundation for future targeted treatment strategies.

PMID:36115922 | DOI:10.1038/s41379-022-01145-0

Health Econ Rev. 2022 Sep 17;12(1):47. doi: 10.1186/s13561-022-00395-7.

ABSTRACT

BACKGROUND: Maternal and neonatal mortality is high in South Asia. Recent studies have identified factors such as adolescent female fertility, healthcare spending is reducing maternal and neonatal mortality. The objective of this study is to examine the effect of adolescent female fertility and healthcare spending on maternal and neonatal mortality in South Asian countries.

METHODS: A retrospective panel study design was used, a total of 8 South Asian countries (Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka) data from World development indicator 1990-2020 considered for analysis. Descriptive statistical method was used for summary. The effect of adolescent female fertility and healthcare spending on maternal and neonatal mortality were analysed using fixed and random effect regression with multiple imputation.

FINDINGS: Adolescent female fertility, maternal, and neonatal mortality is very high in the aforementioned countries, and considerably varies among countries. A significant relationship between the maternal mortality and healthcare spending, neonatal mortality and adolescent female fertility was observed. We found neonatal and maternal mortality are more likely to decrease depends on healthcare spending. Healthcare spending has a significantly negative effect on neonatal mortality (- 0.182, 95% CI: [- 0.295 to -.069]; P-value < 0.01) and maternal mortality (- 0.169, 95% CI: [- 0.243 to – 0.028]; P-value < 0.05). A change in 1 % increases in healthcare spending should decrease by 0.182 neonatal mortality per 1000 live births and maternal mortality by 0.169 per 100,000 live births.

CONCLUSIONS: In south Asian countries, increasing healthcare spending and decreasing adolescent female fertility may contribute to reduce maternal and neonatal mortality. In addition, number of service providers such as physicians supplied contributed to the decline of neonatal mortality. These findings have important implications for future improvement of healthcare spending in maternal and neonatal health programs.

PMID:36115901 | DOI:10.1186/s13561-022-00395-7

Neuropsychol Rev. 2022 Sep 17. doi: 10.1007/s11065-022-09562-3. Online ahead of print.

ABSTRACT

Migraine is a poorly understood neurological disorder and a leading cause of disability in young adults, particularly women. Migraines are characterized by recurring episodes of severe pulsating unilateral headache and usually visual symptoms. Currently there is some disagreement in the electrophysiological literature regarding the universality of all migraineurs exhibiting physiological visual impairments also during interictal periods (i.e., the symptom free period between migraines). Thus, this meta-analysis investigated the evidence for altered visual function as measured electrophysiologically via pattern-reversal visual evoked potential (VEP) amplitudes and habituation in adult migraineurs with or without visual aura and controls in the interictal period. Twenty-three studies were selected for random effects meta-analysis which demonstrated slightly diminished VEP amplitudes in the early fast conducting P100 component but not in N135, and substantially reduced habituation in the P100 and the N135 in migraineurs with and without visual aura symptoms compared to controls. No statistical differences were found between migraineurs with and without aura, possibly due to inadequate studies. Overall, insufficient published data and substantial heterogeneity between studies was observed for all latency components of pattern-reversal VEP, highlighting the need for further electrophysiological experimentation and more targeted temporal analysis of visual function, in episodic migraineurs.

PMID:36115887 | DOI:10.1007/s11065-022-09562-3