The latest medical research on General Medicine / Internal Medicine

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about general medicine / internal medicine gathered by our medical AI research bot.

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Feeding-induced hepatokine, Manf, ameliorates diet-induced obesity by promoting adipose browning via p38 MAPK pathway.

J Exp Med

Activating beige adipocytes in white adipose tissue (WAT) to increase energy expenditure is a promising strategy to combat obesity. We identified t...

The pleiotropic roles of leptin in metabolism, immunity, and cancer.

J Exp Med

The discovery of the archetypal adipocytokine leptin and how it regulates energy homeostasis have represented breakthroughs in our understanding of...

Human KIT+ myeloid cells facilitate visceral metastasis by melanoma.

J Exp Med

Metastasis of melanoma significantly worsens prognosis; thus, therapeutic interventions that prevent metastasis could improve patient outcomes. Her...

PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress.

J Exp Med

Hematopoietic stem cells (HSCs) are capable of entering the cell cycle to replenish the blood system in response to inflammatory cues; however, exc...

The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude.

J Exp Med

Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing ...

Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript.

J Exp Med

Advances in genome sequencing have resulted in the identification of the causes for numerous rare diseases. However, many cases remain unsolved wit...

The Effect of Quadriceps Muscle Length on Maximum Neuromuscular Electrical Stimulation Evoked Contraction, Muscle Architecture, and Tendon-Aponeurosis Stiffness.

Frontiers in Physiology

Muscle-tendon unit length plays a crucial role in quadriceps femoris muscle (QF) physiological adaptation, but the influence of hip and knee angles during QF neuromuscular electrical stimulation (NMES) is poorly investigated. We investigated the effect of muscle length on maximum electrically induced contraction (MEIC) and current efficiency. We secondarily assessed the architecture of all QF constituents and their tendon-aponeurosis complex (TAC) displacement to calculate a stiffness index. This study was a randomized, repeated measure, blinded design with a sample of twenty healthy men aged 24.0 ± 4.6. The MEIC was assessed in four different positions: supine with knee flexion of 60° (SUP60); seated with knee flexion of 60° (SIT60); supine with knee flexion of 20° (SUP20), and seated with knee flexion of 20° (SIT20). The current efficiency (MEIC/maximum tolerated current amplitude) was calculated. Ultrasonography of the QF was performed at rest and during NMES to measure pennation angle (θ p ) and fascicle length (L f ), and the TAC stiffness index. MEIC and current efficiency were greater for SUP60 and SIT60 compared to SUP20 and SIT20. The vastus lateralis and medialis showed lower θ p and higher L f at SUP60 and SIT60, while for the rectus femoris, in SUP60 there were lower θ p and higher L f than in all positions. The vastus intermedius had a similar pattern to the other vastii, except for lack of difference in θ p between SIT60 compared to SUP20 and SIT20. The TAC stiffness index was greater for SUP60. We concluded that NMES generate greater torque and current efficiency at 60° of knee flexion, compared to 20°. For these knee angles, lengthening the QF at the hip did not promote significant change. Each QF constituent demonstrated muscle physiology patterns according to hip and/or knee angles, even though a greater L f and lower θ p were predominant in SUP60 and SIT60. QF TAC index stiffened in more elongated positions, which probably contributed to enhanced force transmission and slightly higher torque in SUP60. Our findings may help exercise physiologist better understand the impact of hip and knee angles on designing more rational NMES stimulation strategies.

www.ClinicalTrials.gov, identifier NCT03822221.

Effects of Allicin on Late Sodium Current Caused by ΔKPQ-SCN5A Mutation in HEK293 Cells.

Frontiers in Physiology

The aim was to study the effect of Allitridum (Allicin) on the heterologous expression of the late sodium current on the ΔKPQ-SCN5A mutations in HEK293 cells, with a view to screening new drugs for the treatment of long QT syndrome type 3 (LQT3).

The ΔKPQ-SCN5A plasmid was transiently transferred into HEK293 cells by liposome technology and administered by extracellular perfusion, and the sodium current was recorded by whole-cell patch-clamp technology. Application of Allicin 30 μM reduced the late sodium current (I Na,L ) of the Nav1.5 channel current encoded by ΔKPQ-SCN5A from 1.92 ± 0.12 to 0.65 ± 0.03 pA/pF (P < 0.01, n = 15), which resulted in the decrease of I Na,L /I Na,P (from 0.94% ± 0.04% to 0.32% ± 0.02%). Furthermore, treatment with Allicin could move the steady-state inactivation of the channel to a more negative direction, resulting in an increase in channel inactivation at the same voltage, which reduced the increase in the window current and further increased the inactivation of the channel intermediate state. However, it had no effect on channel steady-state activation (SSA), inactivation mechanics, and recovery dynamics after inactivation. What's more, the Nav1.5 channel protein levels of membrane in the ΔKPQ-SCN5A mutation were enhanced from 0.49% ± 0.04% to 0.76% ± 0.02% with the effect of 30 mM Allicin, close to 0.89% ± 0.02% of the WT.

Allicin reduced the late sodium current of ΔKPQ-SCN5A, whose mechanism may be related to the increase of channel steady-state inactivation (SSI) and intermediate-state inactivation (ISI) by the drug, thus reducing the window current.

Trial of Psilocybin versus Escitalopram for Depression.

N Engl J

Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking.

In a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a selective serotonin-reuptake inhibitor, over a 6-week period. Patients were assigned in a 1:1 ratio to receive two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo (psilocybin group) or two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram (escitalopram group); all the patients received psychological support. The primary outcome was the change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16; scores range from 0 to 27, with higher scores indicating greater depression) at week 6. There were 16 secondary outcomes, including QIDS-SR-16 response (defined as a reduction in score of >50%) and QIDS-SR-16 remission (defined as a score of ≤5) at week 6.

A total of 59 patients were enrolled; 30 were assigned to the psilocybin group and 29 to the escitalopram group. The mean scores on the QIDS-SR-16 at baseline were 14.5 in the psilocybin group and 16.4 in the escitalopram group. The mean (±SE) changes in the scores from baseline to week 6 were -8.0±1.0 points in the psilocybin group and -6.0±1.0 in the escitalopram group, for a between-group difference of 2.0 points (95% confidence interval [CI], -5.0 to 0.9) (P = 0.17). A QIDS-SR-16 response occurred in 70% of the patients in the psilocybin group and in 48% of those in the escitalopram group, for a between-group difference of 22 percentage points (95% CI, -3 to 48); QIDS-SR-16 remission occurred in 57% and 28%, respectively, for a between-group difference of 28 percentage points (95% CI, 2 to 54). Other secondary outcomes generally favored psilocybin over escitalopram, but the analyses were not corrected for multiple comparisons. The incidence of adverse events was similar in the trial groups.

On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons. Larger and longer trials are required to compare psilocybin with established antidepressants. (Funded by the Alexander Mosley Charitable Trust and Imperial College London's Centre for Psychedelic Research; ClinicalTrials.gov number, NCT03429075.).

Tumor-derived IL-6 and trans-signaling among tumor, fat, and muscle mediate pancreatic cancer cachexia.

J Exp Med

Most patients with pancreatic adenocarcinoma (PDAC) suffer cachexia; some do not. To model heterogeneity, we used patient-derived orthotopic xenogr...

Breaching self-tolerance by targeting the gatekeeper.

J Exp Med

Loss-of-function mutations in DNaseL13, the enzyme that restricts the amount of microparticle-associated DNA, cause SLE in humans and mice. In this...

Evaluation of Time-Limited Trials Among Critically Ill Patients With Advanced Medical Illnesses and Reduction of Nonbeneficial ICU Treatments.

JAMA Internal Medicine

For critically ill patients with advanced medical illnesses and poor prognoses, overuse of invasive intensive care unit (ICU) treatments may prolong suffering without benefit.

To examine whether use of time-limited trials (TLTs) as the default care-planning approach for critically ill patients with advanced medical illnesses was associated with decreased duration and intensity of nonbeneficial ICU care.

This prospective quality improvement study was conducted from June 1, 2017, to December 31, 2019, at the medical ICUs of 3 academic public hospitals in California. Patients at risk for nonbeneficial ICU treatments due to advanced medical illnesses were identified using categories from the Society of Critical Care Medicine guidelines for admission and triage.

Clinicians were trained to use TLTs as the default communication and care-planning approach in meetings with family and surrogate decision makers.

Quality of family meetings (process measure) and ICU length of stay (clinical outcome measure).

A total of 209 patients were included (mean [SD] age, 63.6 [16.3] years; 127 men [60.8%]; 101 Hispanic patients [48.3%]), with 113 patients (54.1%) in the preintervention period and 96 patients (45.9%) in the postintervention period. Formal family meetings increased from 68 of 113 (60.2%) to 92 of 96 (95.8%) patients between the preintervention and postintervention periods (P < .01). Key components of family meetings, such as discussions of risks and benefits of ICU treatments (preintervention, 15 [34.9%] vs postintervention, 56 [94.9%]; P < .01), eliciting values and preferences of patients (20 [46.5%] vs 58 [98.3%]; P < .01), and identifying clinical markers of improvement (9 [20.9%] vs 52 [88.1%]; P < .01), were discussed more frequently after intervention. Median ICU length of stay was significantly reduced between preintervention and postintervention periods (8.7 [interquartile range (IQR), 5.7-18.3] days vs 7.4 [IQR, 5.2-11.5] days; P = .02). Hospital mortality was similar between the preintervention and postintervention periods (66 of 113 [58.4%] vs 56 of 96 [58.3%], respectively; P = .99). Invasive ICU procedures were used less frequently in the postintervention period (eg, mechanical ventilation preintervention, 97 [85.8%] vs postintervention, 70 [72.9%]; P = .02).

In this study, a quality improvement intervention that trained physicians to communicate and plan ICU care with family members of critically ill patients in the ICU using TLTs was associated with improved quality of family meetings and a reduced intensity and duration of ICU treatments. This study highlights a patient-centered approach for treating critically ill patients that may reduce nonbeneficial ICU care.

ClinicalTrials.gov Identifier: NCT04181294.