Nevin Manimala

Exp Physiol. 2022 Sep 18. doi: 10.1113/EP090749. Online ahead of print.

ABSTRACT

NEW FINDINGS: What is the central question of this study? To determine whether the plasma concentration of Notch1 extracellular domain is altered in response to decreased and increased vascular wall shear stress in the forearm, in humans. What is the main finding and its importance? Notch1 extracellular domain is increased with acute increases in antegrade shear rate but does not change with 20 minutes of decreased shear rate caused by distal forearm occlusion. We in turn characterize a novel and integral endothelial mechanosensor in humans that can help explain vascular endothelial adjustments in response to increases in antegrade shear stress.

ABSTRACT: Notch1 has been proposed as a novel endothelial mechanosensor that is central for signalling adjustments in response to changes in vascular wall shear stress. However, there remains no controlled in vivo study in humans. Accordingly, we sought to address the question of whether plasma concentrations of Notch1 extracellular domain (ECD) is altered in response to transient changes in vascular wall shear stress. In 10 young healthy adults (6 M/4F), alterations in shear stress were induced by supra-systolic cuff inflation around the wrist. The opposite arm was treated as a time control with no wrist cuff inflation. Plasma was collected from an antecubital vein of both arms at baseline, 20-min of wrist cuff inflation (low shear), as well as 1-2 min (high shear) and 15-min following wrist cuff release (recovery). The Notch1 ECD was quantified using a commercially available ELISA. Duplex ultrasound was used to confirm alterations in shear stress. In the experimental arm, concentrations of Notch1 ECD remained statistically similar to baseline at all time points except for immediately following cuff release where it was elevated by ∼50% (P = 0.033), coinciding with the condition of high antegrade shear rate. Concentrations of Notch1 ECD remained unchanged in the control arm through all time points. These data indicate that Notch1 is a viable biomarker for quantifying mechanotransduction in response to increased shear stress in humans, and it may underlie the vascular adaptations or mal-adaptations associated with conditions that impact antegrade shear. This article is protected by copyright. All rights reserved.

PMID:36116111 | DOI:10.1113/EP090749

Dent Traumatol. 2022 Sep 18. doi: 10.1111/edt.12789. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: In case of crown fractures after traumatic dental injuries, the affected teeth can be restored either with reattachment of the fractured fragment or with a direct composite restoration. So far, longevity data for reattachments and direct composite restorations with regard to different failure types (pulp necrosis and infection, restoration loss) are scarce. Therefore, the aim of this retrospective study was to evaluate the restorative and biological survival of reattached fragments and composite restorations after crown fractures in permanent teeth.

MATERIAL AND METHODS: Dental records of patients treated between 2000 and 2018 were retrospectively analysed regarding the restoration (reattachment or direct composite restorations) of teeth with crown fractures. Survival (no further intervention) and restorative and/or biological failure of all restored teeth were recorded. Statistical analysis was performed using Kaplan-Meier statistics, and the mean annual failure rates for two and 5 years were calculated. Furthermore, the effect of potential risk factors on survival was assessed. Log-rank tests and univariate Cox regression models (likelihood ratio tests) were used to assess the univariate effect of all variables of interest. Variables with a p-value ≤.10 were included in a multivariate Cox regression model with shared frailty (p < .05).

RESULTS: Overall, 164 patients with 235 teeth (uncomplicated crown fracture: N = 201, complicated crown fracture: N = 34) were included (1.6 ± 2.5 years observation time). Of these, 59 teeth were restored with reattachment of the fragment and 176 with a composite restoration. Overall, composite restorations had a significantly higher survival rate than reattachments (p = .002). The cumulative survival after 2 years was 42.9% and 65.0% for teeth treated with a reattachment (mAFR = 34.5%) and a composite restoration (mAFR = 19.3%), respectively. When differentiating between failure types, restoration failure and pulp necrosis were significantly more frequently detected in reattached crown fractures compared to composite restorations (restorative failure: p = .001; biological failure: p = .036). In the multivariate Cox regression model, the variable jaw and luxation significantly influenced the survival when the tooth was restored with a composite restoration. The survival was not influenced by the fracture type.

CONCLUSIONS: Restorative and biological failures were more frequently detected when the tooth was restored with a reattached fragment compared to a direct composite restoration. Both, restoration failure and pulp necrosis with infection should be considered as frequent complications after restoration of crown-fractured teeth which emphasizes the necessity of regular and short follow-up intervals throughout the first 2 years.

PMID:36116107 | DOI:10.1111/edt.12789

Aust Endod J. 2022 Sep 18. doi: 10.1111/aej.12691. Online ahead of print.

ABSTRACT

Successful root canal treatment requires effective irrigation of the entire root canal system. While chelating agents support irrigation, they can also alter physicochemical properties of the root dentin structure. The aim of this study is to evaluate the effect of different chelation agents on root dentin roughness. Twenty-five extracted maxillary incisors were used in this study. Samples were separated longitudinally and divided into five groups: distilled water, NaOCl, ethylenediaminetetraacetic acid (EDTA), phytic acid and citric acid (CA). Atomic force microscope and energy dispersive X-ray spectroscopy analyses were used for analysing. One-way analysis of variance and Turkey tests were used in the statistical analysis of the study. EDTA, CA and phytic acid solutions increased the roughness and phytic acid and CA solutions decreased the Ca/P ratio in dentin tissue. No statistical difference was observed in the other groups. The decrease of Ca/P ratio should be taken under consideration during irrigation. The increase in surface roughness may provide clinical benefit by supporting the adhesion of the root canal filling materials to the dentin surface.

PMID:36116094 | DOI:10.1111/aej.12691

Updates Surg. 2022 Sep 18. doi: 10.1007/s13304-022-01376-5. Online ahead of print.

ABSTRACT

To evaluate the short- and long-term survival of hyperthermic intraperitoneal chemotherapy (HIPEC) in the patients with advanced gastric cancer (AGC) through randomized controlled trials (RCTs). We analyzed the endpoints of AGC patients including 1-, 2-, 3-, and 5-year overall survival (OS), intestinal anastomotic leakage, myelosuppression, nausea and vomiting from included studies. And we retrieved RCTs from medical literature databases. Risk ratios (RR) was used to calculated the endpoints. Totally, we retrieved 13 articles (14 trial comparisons) which contained 1091 patients. They were randomized to HIPEC group and control group. The results showed that there was no significant differences in survival rates between HIPEC group and control group at 1-, 2- and 3-year follow-up, while a statistical significant overall survival effect was found at the 5-year follow-up [RR: 1.20, 95% CI 1.01 to 1.43, I² = 0.0%]. And there is no significant difference in the risk of intestinal anastomotic leakage, myelosuppression and nausea and vomiting. Compared with the control group, HIPEC could improve the long-term OS without increasing the risk of adverse effect in AGC patients with/without peritoneal carcinomatosis, but there was no benefit at short-term OS.

PMID:36116077 | DOI:10.1007/s13304-022-01376-5

Cancer Causes Control. 2022 Sep 18. doi: 10.1007/s10552-022-01626-2. Online ahead of print.

ABSTRACT

PURPOSE: Neighborhood environments may influence cancer risk. Average population effect estimates might mask differential effects by socioeconomic position. Improving neighborhood environments could inadvertently widen health inequalities if important differences are overlooked.

METHODS: Using linked records of hospital admissions in UK Biobank, we assessed associations between admission with a primary diagnosis of cancer (any/breast/colorectal), and exposure to neighborhood greenspace, physical activity facilities, and takeaway food stores, and whether household income and area deprivation modify these associations. We used adjusted Cox proportional hazards models, and estimated relative excess risks due to interaction (RERI) to assess effect modification.

RESULTS: Associations between neighborhood exposures and cancer-related hospitalizations were weak to null overall, but with some evidence of effect modification. Most notably, more greenspace near home was associated with 16% lower hazard of cancer-related hospital admission in deprived areas (95% CI 2-29%). This was further pronounced for people in low-income households in deprived areas, and for breast cancer.

CONCLUSION: In deprived neighborhoods, increasing the amount of greenspace may help reduce cancer-related hospitalizations. Examining effect modification by multiple socioeconomic indicators can yield greater insight into how social and environmental factors interact to influence cancer incidence. This may help avoid perpetuating cancer inequalities when designing neighborhood environment interventions.

PMID:36116076 | DOI:10.1007/s10552-022-01626-2

J Card Surg. 2022 Sep 18. doi: 10.1111/jocs.16960. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM OF THE STUDY: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery which can result in increased mortality and increased healthcare costs. During Hurricane Maria (2017), a nationwide shortage of mannitol occurred, and our institution switched to the utilization of albumin as a priming fluid solution. We observed decreased rates of POAF during that time and began alternating albumin and mannitol priming fluid solutions. We hypothesized this observation may be from altered perinexal conduction from albumin utilization.

METHODS: A retrospective chart review of all patients from January 2020 through December 2020 who underwent cardiac surgery was performed, to determine if albumin was associated with reduced POAF rates. Two hundred and thirteen patients were identified and 4 were excluded. Two hundred and nine patients (110 albumin priming fluid and 99 mannitol priming fluid) were included in our final analysis.

RESULTS: Analysis was performed for all patients with POAF and in patients with new-onset AF (without a history of prior AF) after surgery. POAF rates showed no statistically significant difference between cohorts. For all patients, POAF occurred in 43% of the albumin subgroup and 47% of the mannitol subgroup (p = .53) and for patients with new-onset AF, POAF occurred in 35% of the albumin subgroup versus 42% of the mannitol subgroup (p = .36). Logistic regression revealed that age, ejection fraction and cardiopulmonary bypass time was associated with POAF, in our cohort.

CONCLUSIONS: The use of albumin compared to mannitol as priming fluid solutions was not associated with statistically significant reductions in POAF rate, in our population.

PMID:36116062 | DOI:10.1111/jocs.16960

J Card Surg. 2022 Sep 18. doi: 10.1111/jocs.16948. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study is to evaluate protamine sulfate effects on graft’s blood flow by comparing transit-time flow measurement (TTFM) values before and after protamine administration.

METHODS: This is an observational study with data collected between years 2018 and 2020. Immediate graft patency was evaluated using TTFM. Only patients with TTFM parameters registered before and after protamine infusion were included. The main three parameters studied were: mean graft flow (MGF), pulsatility index (PI), and diastolic flow (DF). In the first analysis, all conduits were evaluated regardless of the surgical technique used. In a second analysis, on-pump and off-pump groups were compared. Evaluated grafts were left internal thoracic artery, saphenous vein graft (SVG), radial artery, and right internal thoracic artery. Since SVG was numerically the most used graft, an exclusive analysis was created.

RESULTS: Our study included 575 patients, resulting in a total of 1686 grafts, mean 2.93 grafts/patient. Off-pump surgery was performed in 158 patients. Before protamine infusion, inadequate TTFM parameters were observed in 3.8% of grafts. Overall, after protamine administration, MGF decreased in all grafts, but its reduction was not statistically significant. PI values increased in the SVG and DF values reduced in LIMA grafts. SVG group analysis showed that after protamine PI values were higher in OM1 and RCA. DF values increased in RCA. The comparison between off and on-pump surgeries, showed that in off-pump cases TTFM measures did not present statistically significant differences.

CONCLUSION: Significant variations were observed in TTFM values before and after protamine administration. Although different, those values remained within the normal reference ranges. We recommend that flow measurement should be performed before protamine infusion.

PMID:36116058 | DOI:10.1111/jocs.16948

Andrology. 2022 Sep 18. doi: 10.1111/andr.13297. Online ahead of print.

ABSTRACT

BACKGROUND: Alfa-fetoprotein (AFP) is a serum glycoprotein highly produced during fetal development. While AFP synthesis drops dramatically after birth, AFP production only persists or returns under specific pathological condition OBJECTIVE: : We sought to investigate the rate of and the potential meaning of high AFP serum levels in men seeking first medical attention for couple’s primary infertility.

MATERIALS AND METHODS: Socio-demographic and clinical data from 1803 non-Finnish, white-European primary infertile men were retrospectively analysed. AFP was routinely measured in each patient (high AFP was defined as > 7 ng/mL). Men with history of liver diseases, testicular cancer or other known causes of increased AFP levels were excluded from the final analysis. Semen analyses were based on the 2010 WHO reference criteria. Descriptive statistics and logistic regression models tested the association between serum AFP and clinical variables. Possible non-linear relationships were graphically explored with LOESS method.

RESULTS: Overall, high serum AFP level was found in 29 (1,7%) patients. Normal vs. high AFP levels patients were comparable in terms of BMI, CCI, waist circumference, smoking habits, history of cryptorchidism, testicular volume and serum hormones (i.e., FSH, LH and tT). Conversely, men with higher AFP levels were older (p = 0.02), had lower sperm concentration (p = 0,003), and were more frequently oligozoospermic and azoospermic (all p≤0.03). At multivariate analysis, high AFP levels were independently associated with oligozoospermia (OR 3.79; p = 0.033) and azoospermia (OR 3.29; p = 0.006). Likewise, if AFP levels increase, patients were found to be older, with higher BMI and to have more comorbidities (all p<0.05).

DISCUSSION: Unexplained high AFP levels account for almost 2% of cases in primary infertile patients without a previous history of associated disorders. Higher serum AFP levels are linked with aberrant sperm counts, older age, obesity and a greater amount of comorbid conditions.

CONCLUSION: Despite the need for additional validation, these data suggest that serum AFP measurement might have a multifaceted role over the diagnostic work-up of males presenting for couple’s infertility. This article is protected by copyright. All rights reserved.

PMID:36116018 | DOI:10.1111/andr.13297

Ann Clin Transl Neurol. 2022 Sep 17. doi: 10.1002/acn3.51662. Online ahead of print.

ABSTRACT

OBJECTIVE: In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis. While the primary MRI outcome was negative, there was converging neurophysiological and MRI evidence of efficacy. Multiple factors influence lesion remyelination. In this study we undertook a systematic exploratory analysis to determine whether treatment response – measured by change in magnetisation transfer ratio – is influenced by location (tissue type and proximity to CSF) or the degree of abnormality (using baseline magnetisation transfer ratio and T1 values).

METHODS: We examined treatment effects at the whole lesion level, the lesion component level (core, rim and perilesional tissues) and at the individual lesion voxel level.

RESULTS: At the whole lesion level, significant treatment effects were seen in GM but not WM lesions. Voxel-level analyses detected significant treatment effects in WM lesion voxels with the lowest baseline MTR, and uncovered gradients of treatment effect in both WM and CGM lesional voxels, suggesting that treatment effects were lower near CSF spaces. Finally, larger treatment effects were seen in the outer and surrounding components of GM lesions compared to inner cores.

INTERPRETATION: Remyelination varies markedly within and between lesions. The greater remyelinating effect in GM lesions is congruent with neuropathological observations. For future remyelination trials, whole GM lesion measures require less complex post-processing compared to WM lesions (which require voxel level analyses) and markedly reduce sample sizes.

PMID:36116011 | DOI:10.1002/acn3.51662

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