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Nevin Manimala Statistics

Effect of Trypsin Concentration on Living SMCC-7721 Cells Studied by Atomic Force Microscopy

J Microsc. 2021 Aug 5. doi: 10.1111/jmi.13053. Online ahead of print.

ABSTRACT

Trypsin is playing an important role in the processes of cancer proliferation, invasion, and metastasis which require the precise information of morphology and mechanical properties on the nanoscale for the related research. In this work, living human hepatoma (SMCC-7721) cells were treated with different concentrations of trypsin solution. The morphology and mechanical properties of the cells were measured via atomic force microscope (AFM). Statistical analyses of measurement data indicated that with the increase of trypsin concentration, the average cell height and the surface roughness were both increased, but the cell viability, the cell surface adhesion and the elasticity modulus were decreased significantly. The force required to puncture the cells was also gradually reduced. It indicates that trypsin not only hydrolyzes the proteins between the cell and the substrate but also the membrane proteins. The results offer valuable clues for the cancerous process study, pathological analysis, and trypsin inhibitor drug development. And this work provides an effective way for overcoming the cell membrane in drug injection for cell-targeted therapy. This article is protected by copyright. All rights reserved.

PMID:34350998 | DOI:10.1111/jmi.13053

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Nevin Manimala Statistics

Phototherapy With UVB-NB As A New Adjuvant Therapy For Bullous Pemphigoid: A Pilot Study

Photodermatol Photoimmunol Photomed. 2021 Aug 5. doi: 10.1111/phpp.12722. Online ahead of print.

ABSTRACT

Bullous pemphigoid (BP) is an autoimmune blistering skin disease clinically characterized by the development of tense blisters containing serous or hemorrhagic fluid; often patients exhibit a pre-bullous-urticarial eruption and pruritus is a common symptom1 . Since it usually affects the elders, it is often associated with other comorbidities such as diabetes, neurological diseases, internal malignancies and hypertension, and it may be challenging to treat2,3 . The current mainstay of care is topical and/or systemic corticosteroids and immunosuppressants that in the long-term may result in significant morbidity and mortality4 .

PMID:34351011 | DOI:10.1111/phpp.12722

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Development of a clinical practice guideline for weaning and discontinuing parenteral nutrition in hospitalized children as part of a CLABSI-focused quality improvement initiative

JPEN J Parenter Enteral Nutr. 2021 Aug 5. doi: 10.1002/jpen.2247. Online ahead of print.

ABSTRACT

BACKGROUND: Overprescribing of PN increases costs and risks to patients, including from central line-associated blood stream infection (CLABSI). With CLABSI reduction in mind, our children’s hospital began an iterative QI effort to decrease PN utilization by first ensuring appropriate initiation and then defining and ensuring appropriate discontinuation.

MATERIALS AND METHODS: An educational campaign was launched along with audits to evaluate for appropriate PN indications. Next, a literature review was conducted to guide the development of an algorithm to appropriately wean and discontinue PN in pediatric patients. Lastly, all PN discontinuations were audited for agreement with the new guideline. Retrospectively, monthly PN utilization index (orders/patient-days) was plotted on a statistical process control chart to assess change over time. The presence of PN as a risk factor for CLABSI events and the overall hospital CLABSI rate were trended.

RESULTS: Mean PN utilization index fell from 0.156 (July 2018-January 2019) to 0.12 (February 2019-August 2020) (p < 0.01). For 18 months, no PN utilization index reached the baseline lower control limit of 0.144, demonstrating special cause variation and a sustained change. PN as a risk factor for hospital CLABSI cases decreased from most prevalent (49% of cases) to fifth most prevalent (29%), as the CLABSI rate trended down.

CONCLUSION: Engaging frontline staff in the development of a clinical practice guideline and increased accountability to reduce potential patient harm led to a significant and sustained reduction in PN utilization, as well as decreased prevalence of PN as a risk factor in hospital CLABSI cases. This article is protected by copyright. All rights reserved.

PMID:34350991 | DOI:10.1002/jpen.2247

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Low statistical power in a study predicting seizure outcome

Epilepsia. 2021 Aug 5. doi: 10.1111/epi.17030. Online ahead of print.

NO ABSTRACT

PMID:34350995 | DOI:10.1111/epi.17030

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Analysis on the accuracy of CT-guided radioactive I-125 seed implantation with 3D printing template assistance in the treatment of thoracic malignant tumors

J Radiat Res. 2021 Aug 5:rrab068. doi: 10.1093/jrr/rrab068. Online ahead of print.

ABSTRACT

This article analyzes the accuracy of needle track and dose of a 3-dimensional printing template (3DPT) in the treatment of thoracic tumor with radioactive I-125 seed implantation (RISI). A total of 28 patients were included. The technical process included: (i) preoperative CT positioning, (ii) preoperative planning design, (iii) 3DPT design and printing, (iv) 3DPT alignment, (v) puncture and seed implantation. The errors of needle position and dosimetric parameters were analyzed. A total of 318 needles were used. The mean errors in needle depth, needle insertion point, needle tip and needle angle were 0.52 ± 0.48 cm, 3.4 ± 1.7 mm, 4.4 ± 2.9 mm and 2.8 ± 1.7°, respectively. The differences between actual needle insertion angle and needle depth and those designed in the preoperative were statistically significant (p < 0.05). The mean values of all the errors of the chest wall cases were smaller than those of the lungs, and the differences were statistically significant (p < 0.05). There was no significant difference between the D90 calculated in the postoperative plan and those designed in the preoperative and intraoperative plans (p > 0.05). Some dosimetric parameters of preoperative plans such as V100, V200, CI and HI were not consistent with that of preoperative plans, and the difference was statistically significant (p < 0.05). However, there were no statistical difference in the dosimetric parameters between the postoperative plans and intraoperative plans (p > 0.05). We conclude that for thoracic tumors, even under the guidance of 3DPT, there will be errors. The plan should be optimized in real time during the operation.

PMID:34350955 | DOI:10.1093/jrr/rrab068

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Response: “Low statistical power in a study predicting seizure outcome”

Epilepsia. 2021 Aug 5. doi: 10.1111/epi.17029. Online ahead of print.

NO ABSTRACT

PMID:34350989 | DOI:10.1111/epi.17029

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Nevin Manimala Statistics

A Quantitative Systems Pharmacology Framework for Optimal Doxorubicin Granulocyte Colony-Stimulating Factor Regimens in Triple-Negative Breast Cancer

Pharmacology. 2021 Aug 4:1-9. doi: 10.1159/000518037. Online ahead of print.

ABSTRACT

INTRODUCTION: To mitigate the risk of neutropenia during chemotherapy treatment of triple-negative breast cancer, prophylactic and supportive therapy with granulocyte colony-stimulating factor (G-CSF) is administered concomitant to chemotherapy. The proper timing of combined chemotherapy and G-CSF is crucial for treatment outcomes.

METHODS: Leveraging our established mathematical model of neutrophil production by G-CSF, we developed quantitative systems pharmacology (QSP) framework to investigate how modulating chemotherapy dose frequency and intensity can maximize antitumour effects. To establish schedules that best control tumour size while minimizing neutropenia, we combined Gompertzian tumour growth with pharmacokinetic/pharmacodynamic models of doxorubicin and G-CSF, and our QSP model of neutrophil production.

RESULTS: We optimized a range of chemotherapeutic cycle lengths and dose sizes to establish regimens that simultaneously reduced tumour burden while minimizing neutropenia. Our results suggest that cytotoxic chemotherapy with doxorubicin 45 mg/m2 every 14 days provides effective control of tumour growth while mitigating neutropenic risks.

CONCLUSION: This work suggests future avenues for optimal regimens of chemotherapy with prophylactic G-CSF support. Importantly, the algorithmic approach that we developed can aid in balancing the anticancer and the neutropenic effects of both drugs, and therefore contributes to rational considerations in clinical decision-making in triple-negative breast cancer.

PMID:34350894 | DOI:10.1159/000518037

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Effectiveness of Self-Help Plus in Preventing Mental Disorders in Refugees and Asylum Seekers in Western Europe: A Multinational Randomized Controlled Trial

Psychother Psychosom. 2021 Jul 20:1-12. doi: 10.1159/000517504. Online ahead of print.

ABSTRACT

INTRODUCTION: Self-Help Plus (SH+) is a group-based psychological intervention developed by the World Health Organization for managing stress.

OBJECTIVE: To assess the effectiveness of SH+ in preventing mental disorders in refugees and asylum seekers in Western Europe.

METHODS: We conducted a randomized controlled trial in 5 European countries. Refugees and asylum seekers with psychological distress (General Health Questionnaire score ≥3), but without a Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) or ICD/10 diagnosis of mental disorder, as assessed with the Mini International Neuropsychiatric Interview (MINI), were randomized to SH+ or enhanced treatment as usual (ETAU). The primary outcome was the frequency of mental disorders with the MINI at 6 months. Secondary outcomes included the frequency of mental disorders at postintervention, self-identified problems, psychological symptoms, and other outcomes.

RESULTS: Four hundred fifty-nine individuals were randomly assigned to SH+ or ETAU. For the primary outcome, we found no difference in the frequency of mental disorders at 6 months (Cramer V = 0.007, p = 0.90, RR = 0.96; 95% CI 0.52-1.78), while the difference significantly favored SH+ at after the intervention (secondary outcome, measured within 2 weeks from the last session; Cramer V = 0.13, p = 0.01, RR = 0.50; 95% CI 0.29-0.87).

CONCLUSIONS: This is the first randomized indicated prevention study with the aim of preventing the onset of mental disorders in asylum seekers and refugees in Western Europe. As a prevention effect of SH+ was not observed at 6 months, but rather after the intervention only, modalities to maintain its beneficial effect in the long term need to be identified.

PMID:34350902 | DOI:10.1159/000517504

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Endobronchial Valve (Zephyr) Treatment in Homogeneous Emphysema: One-Year Results from the IMPACT Randomized Clinical Trial

Respiration. 2021 Jul 23:1-12. doi: 10.1159/000517034. Online ahead of print.

ABSTRACT

RATIONALE: The long-term safety and effectiveness of bronchoscopic lung volume reduction with Zephyr endobronchial valves in subjects with severe homogeneous emphysema with little to no collateral ventilation beyond 3 months have yet to be established.

METHODS: Ninety-three subjects were randomized to either bronchoscopic lung volume reduction with Zephyr valves or standard of care (SoC) (1:1). Zephyr valve subjects were assessed at 3, 6, and 12 months. SoC subjects were assessed at 3 and 6 months; they were then offered crossover to Zephyr valve treatment.

RESULTS: The mean group difference (Zephyr valve – SoC) for change in FEV1 from baseline to 6 months was 16.3 ± 22.1% (mean ± SD; p < 0.001). Secondary outcomes showed the mean between-group difference for the six-minute walk distance of +28.3 ± 55.3 m (p = 0.016); St. George’s Respiratory Questionnaire, -7.51 ± 9.56 points (p < 0.001); modified Medical Research Council, -0.42 ± 0.81 points (p = 0.019); BODE index, -0.85 ± 1.39 points (p = 0.006); and residual volume of -430 ± 830 mL (p = 0.011) in favor of the Zephyr valve group. At 6 months, there were significantly more responders based on the minimal clinically important difference for these same measures in the Zephyr valve versus the SoC group. The clinical benefits were persistent at 12 months. The percentage of subjects with respiratory serious adverse events was higher in the Zephyr valve group compared to SoC during the first 30 days post-procedure but not statistically different for the Zephyr valve and SoC groups from 31 days to 6 months, and stable in the Zephyr valve group out to 12 months. There were 2 deaths in the SoC group in the 31-day to 6-month period and none in the Zephyr valve group out to 12 months.

CONCLUSIONS: Bronchoscopic lung volume reduction with Zephyr valves in subjects with severe homogeneous emphysema and little to no collateral ventilation provides clinically meaningful change from baseline in lung function, quality of life, exercise capacity, dyspnea, and the BODE index at 6 months, with benefits maintained out to 12 months.

PMID:34350884 | DOI:10.1159/000517034

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Surgical Practice in Girls with Congenital Adrenal Hyperplasia: An International Registry Study

Sex Dev. 2021 Jul 21:1-7. doi: 10.1159/000517055. Online ahead of print.

ABSTRACT

In this article international trends in surgical practice in girls with congenital adrenal hyperplasia (CAH) are evaluated. All cases that had been classified in the I-CAH/I-DSD registry as 46,XX CAH and who were born prior to 2017 were identified. Centers were approached to obtain information on surgical decision making. Of the 330 included participants, 208 (63.0%) presented within the first month of life, and 326 (98.8%) cases were assigned female. Genital surgery had been performed in 250 (75.8%). A total of 64.3, 89.2, and 96.8% of cases residing in Europe, South America and Asia, respectively, had at least one surgery. In a logistic regression model for the probability of surgery before the second birthday (early surgery) over time an increase of probability for early vaginal surgery could be identified, but not for clitoral surgery or both surgeries combined. Genitoplasty in girls with CAH remains controversial. This large international study provides a snapshot of current practice and reveals geographical and temporal differences. Fewer surgeries were reported for Europe, and there seems to be a significant trend towards aiming for vaginal surgery within the first 2 years of life.

PMID:34350892 | DOI:10.1159/000517055