Monday, March 1, 2021

4-Methoxybenzylalcohol protects brain microvascular endothelial cells against oxygen-glucose deprivation/reperfusion-induced injury via activation of the PI3K/AKT signaling pathway

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Exp Ther Med. 2021 Mar;21(3):252. doi: 10.3892/etm.2021.9684. Epub 2021 Jan 24.

ABSTRACT

Damage to the blood-brain barrier (BBB) during the process of cerebral ischemic injury is a key factor that affects the treatment of this condition. The present study aimed to assess the potential effects of 4-methoxybenzyl alcohol (4-MA) on brain microvascular endothelial cells (bEnd.3) against oxygen-glucose deprivation/reperfusion (OGD/Rep) using an in vitro model that mimics in vivo ischemia/reperfusion injury. In addition, the present study aimed to explore whether this underlying mechanism was associated with the inhibition of pro-inflammatory factors and the activation status of the PI3K/Akt signaling pathway. bEnd.3 cells were subjected to OGD/Rep-induced injury before being treated with 4-MA, following which cell viability, lactate dehydrogenase (LDH) release and levels of nitric oxidase (NO) were detected by colorimetry, pro -inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, were detected by ELISA. The expression levels of occluding and claudin-5were evaluated by immunofluorescence staining. The expression levels of AKT, phosphorylated (p)-Akt, endothelial nitric oxide synthase (eNOS) and p-eNOS were also measured by western blot analysis. After bEnd.3 cells were subjected to OGD/Rep-induced injury, cell viability and NO levels were significantly decreased, whilst LDH leakage and inflammatory factor (TNF-α, IL-1β and IL-6) levels were significantly increased. Treatment with 4-MA significantly ameliorated cell viability, LDH release and the levels of NO and pro-inflammatory factors TNF-α, IL-1β and IL-6 as a result of OGD/Rep. Furthermore, treatment with 4-MA upregulated the expression of occludin, claudin-5, Akt and eNOS, in addition to increasing eNOS and AKT phosphorylation in bEnd.3 cells. These results suggest that 4-MA can alleviate OGD/Rep-induced injury in bEnd.3 cells by inhibiting inflammation and by activating the PI3K/AKT signaling pathway as a possible mechanism. Therefore, 4-MA can serve as a potential candidate for treating OGD/Rep-induced injury.

PMID:33613705 | PMC:PMC7856387 | DOI:10.3892/etm.2021.9684

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Challenges of phototherapy for neonatal hyperbilirubinemia (Review)

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Exp Ther Med. 2021 Mar;21(3):231. doi: 10.3892/etm.2021.9662. Epub 2021 Jan 20.

ABSTRACT

Phototherapy is universally recognized as the first option for treating neonatal jaundice due to its unparalleled efficiency and safety in reducing the high serum free bilirubin levels and limiting its neurotoxic effects. However, several studies have suggested that phototherapy may elicit a series of short- and long-term adverse reactions associated with pediatric diseases, including hemolysis, allergic diseases, DNA damage or even cancer. The aim of the present review was to summarize the etiology, mechanism, associated risks and therapeutic strategies for reducing high neonatal serum bilirubin levels. In order to shed light on the negative effects of phototherapy and to encourage implementation of a reasonable and standardized phototherapy scheme in the clinic, the present review sought to highlight the current understanding of the adverse react ions of phototherapy, as it is necessary to further study the mechanism underlying the development of the adverse effects of phototherapy in infants in order to explore novel therapeutic alternatives.

PMID:33613704 | PMC:PMC7859475 | DOI:10.3892/etm.2021.9662

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Al-hijamah (the triple S treatment of prophetic medicine) exerts cardioprotective, tissue-protective and immune potentiating effects in thalassemic children: a pilot clinical trial

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Am J Blood Res. 2020 Dec 15;10(6):447-458. eCollection 2020.

ABSTRACT

Thalassemia is a major health problem in affected children due to iron overload, increased oxidative stress, atherogenic lipid profile and tissue-damage. This study aims at investigating the cardioprotective and tissue-protective benefits of Al-hijamah and their impact on cell-mediated immunity for treating thalassemic children. This study aimed also at investigating the tissue-clearance principle of Taibah mechanism: whenever pathological substances are to be cleared from the human body, Al-hijamah is indicated. Al-hijamah was done to thalassemic children (15 males and 5 females having a mean age of 9.07 ± 4.26 years) using sterile disposable sets in a complete aseptic hospital environment. Prior ethical committee agreement (in addition to written patient's consents) was obtained from Tanta Faculty of Medicine, Egypt. Twenty thalassemic children received iron chela tion therapy plus Al-hijamah for one session (30-60 minutes) versus an age and sex-matched thalassemic control group treated with iron chelation therapy only. Al-hijamah is a quite safe outpatient hematological procedure that significantly decreased serum cholesterol (from 129.75 ± 3.67 to 103.5 ± 4.18 mg/dl) and decreased serum triglycerides (from 109.25 ± 8.96 to 91.95 ± 7.22 mg/dl). Interestingly, Al-hijamah exerted significant tissue-protective effects (it decreased serum GPT from 98.65 ± 12.27 to 71.65 ± 32.78 U/L and serum GOT from 96.35 ± 14.33 to 69.35 ± 34.37 U/L). Al-hijamah-induced ferritin excretion caused decreased serum ferritin (high serum ferritin negatively correlated with cell mediated immunity). Al-hijamah exerted cardioprotective and tissue-protective and hypolipidemic effects. Al-hijamah decreased serum cholesterol and is cardioprotective for thalassemic patients as it protects against atherogenesis and atherosclerosis. Medical practice of Al-hijamah is strongly recommended in hospitals. Al-hijamah cleared blood significantly from causative pathological substances e.g. serum ferritin resulting in enhanced cell-mediated immunity (in agreement with the evidence-based Taibah mechanism).

PMID:33489454 | PMC:PMC7811902

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An unorthodox pathophysiology of severe cases of COVID-19 the weak heme hypothesis

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Am J Blood Res. 2020 Dec 15;10(6):305-310. eCollection 2020.

ABSTRACT

Important amount of severe cases is the main concern in COVID-19 pandemic. It could be the running cause of the burn out of the health system in many countries. The aim of this paper is to suggest a pathophysiologic hypothesis to explain the main characteristics of severe cases of COVID-19 and its underlying conditions. In fact, the clinical and biological picture of severe cases of COVID-19 can easily be explained by free heme toxicity exceeding the endogenous antioxidant systems. Severe cases of COVID-19 are comparable to acute porphyria. On the other hand, the geographical distribution of severe cases of COVID-19 is directly associated to how fresh or polluted the air is. Finally, the relatively low rate of severe cases of COVID-19 could be explained by the presence of an unstable hemoglobin variant highly sensitive to the intrinsic conditions resulting from the a cute pneumonia secondary to SARS-CoV2 infection. The combination of air pollution and free heme toxicity, resulting from the interaction between an unstable hemoglobin variant and SARS-CoV2 infection, seems to be the best scheme to explain clinical and biological manifestations in severe COVID-19. The arguments to support this hypothesis are detailed. We also propose some strategies to verify the concordance of our hypothesis with the reality and the implications it could have, if verified, either for scientists and decision makers.

PMID:33489438 | PMC:PMC7811897

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Lymph Node to Vein Anastomosis (LNVA) for lower extremity lymphedema

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J Plast Reconstr Aesthet Surg. 2021 Jan 30:S1748-6815(21)00048-6. doi: 10.1016/j.bjps.2021.01.005. Online ahead of print.

ABSTRACT

The microsurgical options for lower limb lymphedema is a challenge. In search to improve the overall result, we hypothesized it would be beneficial to add the functioning lymph nodes to vein anastomosis (LNVA) in addition to lymphovenous anastomosis (LVA). This is a retrospective study of 160 unilateral stage II & III lower extremity lymphedema comparing the outcome between the LNVA + LVA group and the LVA only group from May 2013 to June 2018. MRI was used to identify the functioning lymph nodes. Patient outcome, including lower extremity circumference, body weight, bio impedance test, and other data were analyzed to evaluate whether lymph nodes to vein anastomosis (LNVA) improved outcome. The LNVA + LVA group showed significantly better results for circumference reduction rate, body weight reduction r ate, and extracellular fluid reduction rate of the affected limb as compared to the LVA only group for both stage II and III lymphedema. The MRI imaging revealed that 9 cases had no identifiable lymph nodes of the affected limb and 54 cases with a nonfunctioning lymph node upon exploration despite positive imaging. Correlation showed the lymph node size needed to be at least 8 mm in the MRI to be functional. The LNVA + LVA approach for lymphedema has the benefit of better reduction as compared to LVA alone in the lower limb as well as the suprapubic region. Preoperative MRI will help to identify the functioning lymph node by increasing the overall probability of positive outcome.

PMID:33640308 | DOI:10.1016/j.bjps.2021.01.005

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Concurrent chemoradiotherapy with additional chemotherapy for nasopharyngeal carcinoma: A pooled analysis of propensity score‐matching studies

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Abstract

Objective

To determine the benefits of adding induction chemotherapy (IC) and adjuvant chemotherapy (AC) to concurrent chemoradiotherapy (CCRT) for nasopharyngeal carcinoma (NPC) based on propensity score‐matching (PSM) studies.

Methods

Eligible PSM studies were searched in the PubMed, Web of Science, and Embase databases from inception to September 1, 2020. The primary endpoints included overall survival (OS), distant metastasis‐free survival (DMFS), and locoregional recurrence‐free survival (LRFS).

Results

A total of 14 trials consisting of 4086 participants were included. Significant benefits were observed between IC + CCRT and CCRT for OS (hazard ratio [HR], 0.76; 95% confidence interval [CI]: 0.64–0.91) and DMFS (HR, 0.77; 95% CI: 0.64–0.94) with the exception of LRFS (HR, 1.14; 95% CI: 0.90–1.43). However, CCRT + AC did not achieve significant improvements.

Conclusions

IC with CCRT yields significant survival benefits in terms of OS and DMFS, whereas CCRT with AC fails to achieve any additional benefit in all endpoints.

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Survival outcomes in locally advanced cutaneous squamous cell carcinoma presenting with clinical perineural invasion alone

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Abstract

Background

Cutaneous squamous cell carcinomas (CSCC) involving the head and neck are common, but initial presentation or recurrence limited to the cranial nerves is rare.

Methods

We conducted a retrospective study of 21 patients with clinical perineural invasion (PNI) from CSCC and no measurable disease by RECIST 1.1. Patients treated with radiotherapy or chemoradiotherapy were included.

Results

The median time from symptom onset until diagnosis was 13.0 months (2.6–83.1). All patients received radiotherapy. Fourteen received concurrent systemic therapy. The median follow‐up time was 30.5 months (1.1–106.0). Ten patients recurred, with the majority being locoregional. The 2‐year overall survival rate was 85%. The median progression‐free survival (PFS) was 21.5 months with an estimated 2‐year PFS of 44.5% (95%CI: 22.3–66.8).

Conclusions

CSCCs with clinical PNI alone are difficult to diagnose and can have a long interval between appearance of symptoms and diagnosis. They can successfully be treated with chemoradiotherapy. However, many patients still suffer from locoregional recurrences.

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Prevalence and Outcome of Anterior and Middle Cranial Fossae Encephaloceles without Cerebrospinal Fluid Leak or Meningitis

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World Neurosurg. 2021 Jan 30:S1878-8750(21)00119-4. doi: 10.1016/j.wneu.2021.01.088. Online ahead of print.

ABSTRACT

BACKGROUND: With advances in imaging techniques, encephaloceles, meningoceles, and meningoencephaloceles are occasionally discovered incidentally. These can be located in anterior cranial fossa (ACF), mostly protruding into sphenoid and ethmoid sinuses, or middle cranial fossa (MCF), protruding into the temporal bone. We reviewed a large series of cranial computed tomography and magnetic resonance imaging scans to identify the prevalence of asymptomatic encephaloceles, meningoceles, and meningoencephaloceles and describe their outcome.

METHODS: We retrospectively reviewed a database of all magnetic resonance imaging and computed tomography scans done at Weill Cornell Medicine for any reason between 2003 and 2018. Encephaloceles, meningoceles, or meningoencephaloceles were confirmed on 72 scans. Of these, chart reviews wer e performed to identify incidentally discovered cases with symptoms other than cerebrospinal fluid leak, and chart reviews and phone calls were conducted to determine patient demographics, treatment, and outcome.

RESULTS: There were 18 incidental cases for a prevalence of 0.0074%, of which 6 were located in ACF, and 12 were located in MCF. The mean age for ACF cases was 39 ± 15.9 years and for MCF cases was 49.5 ± 19.8 years. There were no leaks in any cases after the encephaloceles were discovered. Eleven of 12 (91.6%) MCF cases were treated conservatively, while 3 of 6 (50%; P = 0.083) ACF cases were treated surgically.

CONCLUSIONS: This study showed that encephaloceles, meningoceles, and meningoencephaloceles without cerebrospinal fluid leak or meningitis in MCF were more often conservatively managed with observation only, whereas these entities in ACF were often repaired prophylactically. Incidentally discovered encephaloceles have a relatively benign natural histo ry and do not precipitously leak.

PMID:33529766 | DOI:10.1016/j.wneu.2021.01.088

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Peristapedial bulb: an indicator of spontaneous CSF leak in cochlear candidates with Mondini dysplasia

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Acta Otolaryngol. 2021 Feb 27:1-6. doi: 10.1080/00016489.2021.1887930. Online ahead of print.

ABSTRACT

BACKGROUND: Mondini dysplasia with spontaneous cerebrospinal fluid (CSF) leak is rare in cochlear implantation (CI) candidates but lethal. Detailed evaluation and surgical intervention are needed for these patients.

AIM/OBJECTIVE: To report our findings of the peristapedial bulb in computer tomography (CT) as diagnostic evidence of spontaneous CSF leak and discuss its clinical value to direct the surgical plan for patients with profound sensorineural hearing loss (SNHL) and meningitis.

MATERIAL AND METHODS: A retrospective review was conducted, including patients' demographic features, radiographic examination, operation records, auditory/speech evaluation. The patients presented with a peristapedial bulb were included.

RESULTS: In 2775 CI recipients, 7 out of 219 (3.2%) patients with Mondini anomaly had detectable peristap edial bulbs in HRCT, among whom 6 patients have a history of meningitis. Surgical exploration verified the radiographic findings in 6 out of 7 patients. All patients received CI and vestibular obliteration. Control of meningitis was acceptable. The threshold of hearing significantly decreased from 74.1 dB ± 6.9 dB to 37.1 ± 4.8 dB after CI and the word recognition score elevated from 21.4 ± 14.9% to 78.6 ± 9.3%.

CONCLUSIONS AND SIGNIFICANCE: Peristapedial bulb is an indicator of spontaneous CSF leak in patients with profound SHNL and Mondini anomaly. Patients will benefit from CI and surgical intervention.

PMID:33641594 | DOI:10.1080/00016489.2021.1887930

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New drug approval: Olaparib and niraparib - first line in ovarian cancer

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Bull Cancer. 2021 Feb 25:S0007-4551(21)00038-2. doi: 10.1016/j.bulcan.2021.01.003. Online ahead of print.

NO ABSTRACT

PMID:33641880 | DOI:10.1016/j.bulcan.2021.01.003

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The Optimal Activity of Radioactive Iodine for Remnant Ablation in Low/Intermediate Risk Differentiated Thyroid Carcinoma: A Continuous Controversy and Meta-Analysis

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Cureus. 2021 Jan 27;13(1):e12937. doi: 10.7759/cureus.12937.

ABSTRACT

Radioactive iodine (RAI) is widely used for remnant ablation in low/intermediate differentiated thyroid carcinoma (DTC). However, the optimal effective dose that overweighs the benefits over unwanted side effects is a matter of controversy. This meta-analysis aimed to assess low versus high doses of RAI activity for DTC remnant ablation. Two authors independently searched PubMed and Cochrane Library using the key words low dose radioactive iodine, high dose radioactive iodine, low-risk/intermediate risk, differentiated thyroid carcinoma, and remnant ablation. Two hundred and twenty references were identified when limiting the engine to controlled trials in English and during the period from January 2010 to December 2020. Nine trials (five from Europe and four from Asia) including 3137 patients fulfilled the inclusion and exclusion criteria. The data were then entered in an extraction sheet detailing the trial information including the author's name, year of publication, country, and type of surgery, preparation for RAI, the patients and control number in the low and high-dose groups, follow-up period, and the results. Out of 220 articles retrieved, nine controlled trials were included (follow-up period range, six months to 12 years, 3137 patients, and low risk of bias). The analysis favored the high dose for remnants ablation, odd ratio, 0.73, 95% CI, 0.50-1.07; P-value for the overall effect was 0.10. However, the results were limited due to the significant heterogeneity observed (56%, P-value 0.03). High-dose RAI was better for DTC remnants ablation. Further studies focusing on intermediate-risk DTC and adjusting for preoperative and postoperative factors are recommended.

PMID:33643743 | PMC:PMC7885745 | DOI:10.7759/cureus.12937

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