Precise measurement of molecular phenotypes with barcode-based CRISPRi systems.

Genome-wide CRISPR-Cas9 screens have untangled regulatory networks and revealed the genetic underpinnings of diverse biological processes. Their success relies on experimental designs that interrogate specific molecular phenotypes and distinguish key regulators from background effects. Here, we realize these goals with a generalizable platform for CRISPR interference with barcoded expression reporter sequencing (CiBER-seq) that dramatically improves the sensitivity and scope of genome-wide screens.

Molecular recording of calcium signals via calcium-dependent proximity labeling.

Calcium ions serve as key intracellular signals. Local, transient increases in calcium concentrations can activate calcium sensor proteins that in turn trigger downstream effectors. In neurons, calcium transients play a central role in regulating neurotransmitter release and synaptic plasticity.

Intravenous dexamethasone in pain treatment after video-assisted thoracoscopic surgery.

Introduction: Video-assisted thoracoscopic surgery (VATS) is a minimally invasive procedure. Despite being less invasive than thoracotomy, post-operative pain remains a significant clinical problem. The aim of this study was to investigate if perioperative intravenous (IV) dexamethasone improves pain management in VATS.

Defining the mechanisms and properties of post-transcriptional regulatory disordered regions by high-throughput functional profiling.

Disordered regions within RNA binding proteins are required to control mRNA decay and protein synthesis. To understand how these disordered regions modulate gene expression, we surveyed regulatory activity across the entire disordered proteome using a high-throughput functional assay. We identified hundreds of regulatory sequences within intrinsically disordered regions and demonstrate how these elements cooperate with core mRNA decay machinery to promote transcript turnover.

Clinical impact of Bachmann's bundle pacing defined by electrocardiographic criteria on atrial arrhythmia outcomes.

Aims: Evaluate whether Bachmann's bundle pacing (BBp) defined by electrocardiographic (ECG) criteria is associated with less atrial fibrillation/tachycardia (AF/AT) compared with anatomically defined right atrial septal pacing (RASp) and right atrial appendage pacing (RAAp).

Methods And Results: This is a retrospective study comparing BBp with non-specific RASp and RAAp on new incidence, burden, and recurrence of AF/AT. We included patients who underwent atrial lead placement between 2006 and 2019 and received > 20% atrial pacing.

Cerebellar infarction requiring surgical decompression in patient with COVID 19 pathological analysis and brief review.

Background: This report and literature review describes a case of a COVID-19 patient who suffered a cerebellar stroke requiring neurosurgical decompression. This is the first reported case of a sub-occipital craniectomy with brain biopsy in a COVID-19 patient showing leptomeningeal venous intimal inflammation.

Clinical Description: The patient is a 48-year-old SARS-COV-2 positive male with multiple comorbidities, who presented with fevers and respiratory symptoms, and imaging consistent with multifocal pneumonia.

Pdc2/Pat1 increases the range of decay factors and RNA bound by the Lsm1-7 complex.

Pat1, known as Pdc2 in fission yeast, promotes the activation and assembly of multiple proteins during mRNA decay. After deadenylation, the Pat1/Lsm1-7 complex binds to transcripts containing oligo(A) tails, which can be modified by the addition of several terminal uridine residues. Pat1 enhances Lsm1-7 binding to the 3' end, but it is unknown how this interaction is influenced by nucleotide composition.

Pat1 activates late steps in mRNA decay by multiple mechanisms.

Pat1 is a hub for mRNA metabolism, acting in pre-mRNA splicing, translation repression, and mRNA decay. A critical step in all 5'-3' mRNA decay pathways is removal of the 5' cap structure, which precedes and permits digestion of the RNA body by conserved exonucleases. During bulk 5'-3' decay, the Pat1/Lsm1-7 complex engages mRNA at the 3' end and promotes hydrolysis of the cap structure by Dcp1/Dcp2 at the 5' end through an unknown mechanism.

Minimally invasive transpedicular vertebrectomy for metastatic disease to the thoracic spine.

Study Design And Objective: We present a series of 8 patients with thoracic metastatic disease causing acute neurologic decline. We present minimally invasive posterolateral vertebrectomy and decompression as an effective approach in patients with significant comorbidities and as palliative care.

Background: Metastatic disease to the spine is common and frequently occurs in the thoracic vertebrae.

Successful prophylactic treatment for bleeding in a girl with severe hereditary prothrombin deficiency using a prothrombin complex concentrate (Bebulin VH).

The authors describe the evaluation and course of severe hereditary prothrombin deficiency in a 14-year-old girl first diagnosed at age 4 years. Detailed is the evolution of her treatment from episodic fresh-frozen plasma after bleeding events to prophylactic home infusions with the prothrombin complex concentrate Bebulin VH. Pharmacokinetic data on factor II recovery and half-life are presented.

2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) in a nude rat glioma model: implications for photodynamic therapy.

Background And Objective: In this study, we evaluated 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-alpha (HPPH or Photochlor) as a photosensitizer for the treatment of malignant gliomas by photodynamic therapy (PDT).

Study Design/materials And Methods: We performed in vivo reflection spectroscopy in athymic rats to measure the attenuation of light in normal brain tissue. We also studied HPPH pharmacokinetics and PDT effects in nude rats with brain tumors derived from stereotactically implanted U87 human glioma cells.

Focal enhancement of cranial nerve V after radiosurgery with the Leksell gamma knife: experience in 15 patients with medically refractory trigeminal neuralgia.

Background And Purpose: Gamma knife radiosurgery is an alternative for the treatment of medically refractory trigeminal neuralgia. Few reports of posttreatment MR imaging appearance of cranial nerve V exist. Our purpose was to define MR imaging characteristics in cranial nerve V after gamma knife radiosurgery.

Constitutional inversion of chromosome 7 and hematologic cancers.

Nonrandom aberrations of chromosome 7 have been described in various hematopoietic disorders. We describe here two unrelated families with the same constitutional inversion of chromosome 7 [inv(7)(q11.2q22)].

Interleukin-6-associated laboratory parameters and immunohistochemistry in symptomatic stage A and B nodular sclerosing Hodgkin's disease in children.

Interleukin (IL)-6-associated laboratory parameters obtained at diagnosis on 17 children with histologically confirmed nodular sclerosing Hodgkin's disease (NSHD) are reported. When these patients were grouped as either symptomatic stage A or B, they were found to be similar in extent of disease, age, and gender. However, statistically significant differences between these two groups were observed for the means of the following IL-6-associated laboratory parameters: hematocrit (p = 0.

Aluminum-induced microcytosis in a child with moderate renal insufficiency.

A child with moderate renal failure, on high doses of aluminum compounds for treatment for hyperphosphatasemia, presented with unexplained microcytosis. The patient also had psychomotor delay. On discontinuation of aluminum, microcytosis reversed in 2 months.

Value of screening umbilical cord blood for hemoglobinopathy.

Foremost among the beneficial effects of screening umbilical cord blood is the optimized quality of care that can follow the immediate involvement of an infant with sickle cell disease and his or her family in an appropriate health care system. This is exemplified by the reduction in the case fatality rate of pneumococcal septicemia that has been achieved. Appropriate follow-up of screening also includes transmission of information about the diagnosis of a hemoglobinopathy trait or alpha-thalassemia to affected families and their physicians, with ready availability of education and counseling.

Hemodynamic response to exercise in patients with sickle cell anemia.

In order to evaluate potential electrocardiographic (ECG) correlates of ST-segment depression during exercise in patients with sickle cell anemia (SS), 43 subjects, aged 5-23 years, underwent submaximal exercise testing. Eight (19%) had ST-segment depression on the exercise ECG during submaximal exercise. These eight patients had significantly lower hemoglobin levels than the 35 subjects without evidence of ST-segment depression.

Parvovirus B19 infection associated with reticulocytopenia and chronic autoimmune hemolytic anemia.

A previously healthy 11-year-old white female presented with a Coomb's positive hemolytic anemia and reticulocytopenia. The patient was treated with prednisone (6.4 mg/kg/day) and had a stable hemoglobin with subsequent recovery of reticulocytes by 7 days.

Distal CCAAT box deletion in the A gamma globin gene of two black adolescents with elevated fetal A gamma globin.

Point mutations in G gamma and A gamma globin gene promoters are associated with increased production of G gamma and A gamma globin, respectively. To determine whether an upstream promoter mutation could account for elevated A gamma in a Black adolescent with A gamma-beta+-HPFH and sickle cell trait, we cloned the 13 kb BglII fragment containing both gamma genes into phage lambda vector EMBL3. For one clone, the A gamma upstream promoter showed no hybridization to a 19 bp oligonucleotide whose sequence centered at -117.

Severe anemia caused by human parvovirus in a leukemia patient on maintenance chemotherapy.

A 6-year-old boy on maintenance chemotherapy for acute lymphocytic leukemia developed severe hypoplastic anemia during chemotherapy previously well tolerated. The hypoplastic episode persisted for approximately 30 days. Human parvovirus (B19), the etiologic agent of aplastic crisis in persons with underlying hemolytic syndromes, was detected in the patient's serum 25-30 days after onset of hemoglobin decrease, and B19 IgM seroconversion occurred 1 week later.

Methemoglobinemia and hemolytic anemia associated with Campylobacter jejuni enteritis.

A 7-week-old infant with methemoglobinemia, hemolytic anemia, and inadequate weight gain was found to have a Campylobacter jejuni gastrointestinal tract infection. Known etiologies of methemoglobinemia such as oxidative drug exposure, deficiency of NADH-methemoglobin reductase, and hemoglobin M disorder were excluded. The patient had a twin brother (probably identical) who had neither methemoglobinemia nor stool cultures positive for C.

Pregnancy associated with both insulin-dependent diabetes mellitus and sickle cell disease. A report of two cases.

Two pregnant women were treated for both insulin-dependent diabetes and sickle cell disease. Careful application of treatments developed for each of these conditions allowed both pregnancies to be successfully carried to term.

Direct evidence that decreased serum opsonization of Streptococcus pneumoniae via the alternative complement pathway in sickle cell disease is related to antibody deficiency.

Two approaches were used to demonstrate that reduction in serum opsonization of Streptococcus pneumoniae via the alternative complement pathway in children with sickle cell disease is related to a deficiency of antibodies to pneumococcal capsular polysaccharide. First, opsonization of S. pneumoniae mediated by the alternative pathway in patients' sera was restored to normal by addition of the purified IgG or IgM fraction of goat antiserum to capsular polysaccharide of the homologous serotype.