Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis.

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs.

Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India.

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), β-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile.

Role of Iron Therapy in Heart Failure: A Consensus Statement from India.

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF.

"You're stuck in the middle here": a qualitative study of GPs' experiences of managing knee pain attributed to a degenerative meniscal tear.

Background: Exercise is the recommended first-line therapy for a degenerative meniscal tear (DMT). Despite this, knee pain attributed to DMTs are a common presentation to specialist orthopaedic clinics. In the primary care setting, the general practitioner (GP) plays a central role in managing patients with knee pain, but to date their perspective has not been explored in relation to DMTs.

The Accuracy of Ultrasound Controlled Attenuation Parameter in Diagnosing Hepatic Fat Content.

Purpose: The Controlled Attenuation Parameter (CAP score) is based on ultrasonic properties of retropropagated radiofrequency signals acquired by Fibroscan (Echosens, Paris, France). Since ultrasound propagation is influenced by the presence of fat, CAP score was developed to quantify steatosis. The aim of this study was to delineate the accuracy of CAP in diagnosing hepatic steatosis, compared to the gold standard of liver biopsy.

Avelumab in Patients With Metastatic Colorectal Cancer.

Background: Metastatic colorectal cancer (mCRC) is incurable, and median overall survival is less than 2½ years. Although monoclonal antibodies that block PD-1/PD-L1 interactions are active in microsatellite unstable/mismatch repair deficient tumors, a growing dataset shows that most patients with microsatellite stable/mismatch repair proficient tumors will not benefit from the blockade of PD-1/PD-L1 interactions. Here we present results from patients with mCRC (n = 22) treated with the anti-PD-L1 monoclonal antibody avelumab.

A pentasaccharide for monitoring pharmacodynamic response to gene therapy in GM1 gangliosidosis.

Background: GM1 gangliosidosis is a rare, fatal, neurodegenerative disease caused by mutations in the GLB1 gene and deficiency in β-galactosidase. Delay of symptom onset and increase in lifespan in a GM1 gangliosidosis cat model after adeno-associated viral (AAV) gene therapy treatment provide the basis for AAV gene therapy trials. The availability of validated biomarkers would greatly improve assessment of therapeutic efficacy.

Chediak-Higashi syndrome.

Purpose Of Review: Chediak-Higashi syndrome is a rare autosomal recessive disorder characterized by congenital immunodeficiency, bleeding diathesis, pyogenic infection, partial oculocutaneous albinism, and progressive neurodegeneration. Treatment is hematopoietic stem cell transplantation or bone marrow transplantation; however, this does not treat the neurologic aspect of the disease. Mutations in the lysosomal trafficking regulator (LYST) gene were identified to be causative of Chediak-Higashi, but despite many analyses, there is little functional information about the LYST protein.

A comparative randomized controlled study of modified 4 in 1 block versus IPACK plus adductor canal block for post-operative analgesia in total knee arthroplasty.

Background And Aims: Postoperative analgesia for Total Knee Arthroplasty (TKA) is paramount for early mobilisation and rehabilitation. The newer motor sparing peripheral nerve blocks for analgesia for TKA are 4 in 1 block, modified 4 in 1 block, infiltration between popliteal artery and capsule of the knee (IPACK) block along with adductor canal block (ACB). We hypothesised that Modified 4 in 1 block is as efficient as the already proven technique of combined IPACK and ACB in providing post-operative analgesia to the patients of TKA.

Project Tooth Fairy: a pan-London initiative from conception to delivery to patient-reported experience measures.

Pressure on paediatric dental general anaesthetic (GA) waiting lists has recently been at its highest, further compounded by the COVID-19 pandemic. Project Tooth Fairy (PTF), a pan-London collaborative project, was conceived in response to this backlog. A dedicated day case GA suite was established within The Royal London Dental Hospital (Barts Health NHS Trust) for use by multiple trusts to enhance elective recovery.

Pulmonary function and structure abnormalities in children and young adults with osteogenesis imperfecta point to intrinsic and extrinsic lung abnormalities.

Purpose: Pulmonary disease is the major cause of morbidity and mortality in osteogenesis imperfecta (OI). We investigated the contribution of intrinsic lung factors to impaired pulmonary function in children and young adults with OI types III, IV, VI.

Methods: Patients with type III (n=8), IV (n=21), VI (n=5), VII (n=2) or XIV (n=1) OI (mean age 23.

Neuronal Spiking Responses to Direct Electrical Microstimulation in the Human Cortex.

Microstimulation can modulate the activity of individual neurons to affect behavior, but the effects of stimulation on neuronal spiking are complex and remain poorly understood. This is especially challenging in the human brain where the response properties of individual neurons are sparse and heterogeneous. Here we use microelectrode arrays in the human anterior temporal lobe in 6 participants (3 female) to examine the spiking responses of individual neurons to microstimulation delivered through multiple distinct stimulation sites.

Lateralization of interictal temporal lobe hypoperfusion in lesional and non-lesional temporal lobe epilepsy using arterial spin labeling MRI.

Purpose: Non-invasive imaging studies play a critical role in the presurgical evaluation of patients with drug-resistant temporal lobe epilepsy (TLE), particularly in helping to lateralize the seizure focus. Arterial Spin Labeling (ASL) MRI has been widely used to non-invasively study cerebral blood flow (CBF), with somewhat variable interictal alterations reported in TLE. Here, we compare temporal lobe subregional interictal perfusion and symmetry in lesional (MRI+) and non-lesional (MRI-) TLE compared to healthy volunteers (HVs).

Investigating the relationship between early life adversity, inflammation and alcohol use.

Early life adversity (ELA) has long-lasting and potentially harmful effects on adult mental and physical health, including a higher likelihood of developing psychiatric conditions such as depression, anxiety and alcohol use disorder (AUD). It has been suggested that inflammation may play a role in linking ELA to the development of AUD. Here, we evaluated a number of predictive factors of high sensitivity C-reactive protein (hsCRP), a key inflammatory marker, and the potential mediating role of hsCRP in the relationship between ELA and alcohol misuse in adulthood.