Notes

Phenolic materials and also cyanogenesis in galled along with non-galled tissues from the fern species Microgramma vacciniifolia.
Afatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its 'real-world' safety and efficacy.

EGFR-TKI treatment-naïve patients with EGFR mutation-positive NSCLC received afatinib 40 mg/day until disease progression or other withdrawal criteria. Dose reductions were permitted for adverse events (AEs). The primary endpoint was the number of patients with AEs (CTCAE version 3.0). Other endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and changes in investigator-assessed cancer-related symptoms.

Eighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9-23.3 months). Grade 3 treatment-related AEs (TRAEs) were reported in 51 (58%) patients; the most common were diarrhea (22%) and rash/acne (20%). No grade > 3 TRAEs were reported. AEs leading to dose reduction occurred in 49 (56%) patients. Treatment discontinuation due to TRAEs occurred in 4 (5%) patients. ORR was 81% overall, 89% in patients with brain metastases, and 55% in patients with uncommon mutations (excluding T790M/exon 20 insertions). Median DOR was 15.1 months (95% CI 12.4-21.4 months). Cancer-related symptoms were improved/unchanged/worsened in 34-66%/36-66%/0-3% of patients over the first year.

No unexpected safety signals for afatinib were observed. AEs were manageable; the treatment discontinuation rate was low. Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations.

ClinicalTrials.gov NCT01931306 ; 29/08/2013.
ClinicalTrials.gov NCT01931306 ; 29/08/2013.
Although the major anticancer effect of metformin involves AMPK-dependent or AMPK-independent mTORC1 inhibition, the mechanisms of action are still not fully understood.

To investigate the molecular mechanisms underlying the effect of metformin on the mTORC1 inhibition, MTT assay, RT-PCR, and western blot analysis were performed.

Metformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity. Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment. Moreover, REDD1- and Sestrin2-mediated mTORC1 inhibition in response to metformin was independent of AMPK activation. Additionally, lapatinib enhances cell sensitivity to metformin, and knockdown of REDD1 and Sestrin2 decreased cell sensitivity to metformin and lapatinib.

ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.
ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.
Severity of symptoms in patients with schizophrenia is a determinant of patient's well-being, but evidence in low- and middle-income countries is limited. We aimed to measure the symptom severity using objective measurements, the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity scale (CGI-S), and their associations with well-being in patients with schizophrenia.

Patients with schizophrenia aged ≥18 years, without active psychosis including no history of hospitalization within the last 6 months, were included. Symptom severity was measured by the clinicians using BPRS and CGI-S. The patients' well-being was assessed by self-report using the Subjective Well-being under Neuroleptic treatment scale (SWN) as continuous and binary outcomes (categorized into adequate or poor well-being). Correlations between symptom severity (BPRS and CGI-S scores) and well-being (SWN score) were analyzed using Pearson's correlation. Association between well-being status and BPRS was analyzed using mociated with lower patients' well-being. The use of BPRS tool into routine clinical practice could serve as an adjunct to physician's clinical evaluation of patients' symptoms and may help improve patient's well-being. Further research on negative symptoms associated with well-being is required.
Mental-somatic multimorbidity in general hospital settings is associated with long hospital stays, frequent rehospitalization, and a deterioration of disease course, thus, highlighting the need for treating hospital patients more holistically. However, there are several challenges to overcome to address mental health conditions in these settings. This study investigated hospital personnel's perceived importance of and experiences with mental-somatic multimorbidities of patients in hospital settings in Basel, Switzerland, with special consideration of the differences between physicians and nurses.

Eighteen semi-structured interviews were conducted with nurses (n= 10) and physicians (n= 8) in different hospitals located in Basel, Switzerland. An inductive approach of the framework analysis was used to develop the themes.

Four themes emerged from the data analysis 1) the relevance of mental-somatic multimorbidity within general hospitals, 2) health professionals managing their emotions towards mental healt stronger focus should be placed on physicians to improve their competencies in considering patient mental health in their daily somatic treatment care.
To report Stevens-Johnson syndrome (SJS) in a patient with acute pneumonia secondary to SARS-CoV-2 infection.

A 45-years-old woman with a diagnosis of acute pneumonia secondary to SARS-CoV-2 infection who had received azithromycin and naproxen. Tamoxifen in vivo Three days after starting the medication, she appeared ill and developed ocular discomfort, photophobia, dysuria, and macular rashes on the trunk and the extremities. On ophthalmological examination, a total epithelial defect was seen in both eyes. According to the examination, Stevens-Johnson syndrome was diagnosed and the patient was admitted to receive systemic and ocular support and medical care. The patient's condition improved during the 3 weeks and recovered from both COVID-19 and SJS life-threatening complications but ocular complications, including the destruction of the meibomian glands, irregularity of the eyelid margin, and corneal scarring remained for the patient.

Although, it is not clear whether the cause of Stevens-Johnson syndrome in COVID-19 patients is the virus itself or whether the use of medication, but patients with COVID-19, especially patients receiving medication, should be screened for symptoms of Stevens-Johnson syndrome.
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