Efficacy of non-surgical, non-pharmacological treatments for congenital muscular torticollis: a systematic review and meta-analysis.

Background: Congenital Muscular Torticollis (CMT) is the third most common musculoskeletal condition in infancy, and if untreated can lead to significant disability. While a range of conservative treatments are commonly used in the management of CMT, an understanding of their efficacy and safety is limited. This systematic review and meta-analysis, without language or discipline restriction, was conducted to address this knowledge gap.

Soluble Fms-like tyrosine kinase-1 polymorphisms associated with severe-spectrum hypertensive disorders of pregnancy.

Background: sFLT-1 has been implicated in the pathogenesis of HDP. We aimed to examine the role of maternal and fetal polymorphisms in risk of HDP and severe-spectrum disease.

Methods: Cases of HDP (143) and controls (169) from mother-baby dyads were recruited at the Los Angeles County Women's and Children's Hospital (WCH).

Preclinical Safety Assessment of the EBS-LASV Vaccine Candidate against Lassa Fever Virus.

There are currently no prophylactic vaccines licensed to protect against Lassa fever caused by Lassa virus (LASV) infection. The Emergent BioSolutions (EBS) vaccine candidate, EBS-LASV, is being developed for the prevention of Lassa fever. EBS-LASV is a live-attenuated recombinant Vesicular Stomatitis Virus (rVSV)-vectored vaccine encoding the surface glycoprotein complex (GPC) from LASV and has two attenuating vector modifications: a gene shuffle of the VSV N gene and a deletion of the VSV G gene.

Potential value of animal microphysiological systems.

Microphysiological systems (MPS) are designed to recapitulate aspects of tissue/organ physiology in vivo, thereby providing potential value in safety and efficacy assessments of FDA-regulated products and regulatory decision-making. While there have been significant advances in the development, use, and proposals of qualification criteria for human organ MPS, there remains a gap in the development using animal tissues. Animal MPS may be of value in many areas including the study of zoonotic diseases, assessment of the safety and efficacy of animal therapeutics, and possibly reduction of the use of animals in regulatory submissions for animal therapeutics.

Roots, Leaves, and Flowers: A Narrative Review of Herbs and Botanicals Used for Self-Managed Abortion in Asia and the Pacific.

Abortion has existed throughout history, often outside of formal health care systems. This type of care, now called self-managed abortion, has historically been achieved in part through botanicals and traditional medicines. Their use continues into the modern day, especially in Asia, Hawai'i, and other Pacific Islands, where indigenous medicine traditions practice alongside allopathic medicine.

Remote Provision of Medication Abortion and Contraception Through Telemedicine.

This Narrative Review describes the remote provision of family planning services, including medication abortion and contraception, through telemedicine. The coronavirus disease 2019 (COVID-19) pandemic was a catalyst to shift toward telemedicine to maintain and expand access to crucial reproductive health services when public health measures necessitated social distancing. There are legal and political considerations when providing medication abortion through telemedicine, along with unique challenges, even more so after the Dobbs decision starkly limited options for much of the country.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for a soluble glycoprotein vaccine to prevent disease caused by Nipah or Hendra viruses.

Auro Vaccines LLC has developed a protein vaccine to prevent disease from Nipah and Hendra virus infection that employs a recombinant soluble Hendra glycoprotein (HeV-sG) adjuvanted with aluminum phosphate. This vaccine is currently under clinical evaluation in a Phase 1 study. The Benefit-Risk Assessment of VAccines by TechnolOgy Working Group (BRAVATO; ex-V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of protein vaccines.

COVID-19 pneumonia in kidney transplant recipients: Focus on immunosuppression management.

Background: The coronavirus disease of 2019, also known as COVID-19, has been declared a global pandemic. Significant controversies exist regarding treatment modalities for this novel disease, especially in immunocompromised patients. Experience with management of COVID-19 in kidney transplant recipients is scarce; effects of this virus on immunosuppressed individuals are not well understood.

Rates of Maternal and Perinatal Mortality and Vertical Transmission in Pregnancies Complicated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co-V-2) Infection: A Systematic Review.

Objective: To ascertain the frequency of maternal and neonatal complications, as well as maternal disease severity, in pregnancies affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Data Sources: MEDLINE, Ovid, ClinicalTrials.gov, MedRxiv, and Scopus were searched from their inception until April 29, 2020.

Safety and immunogenicity of a highly attenuated rVSVN4CT1-EBOVGP1 Ebola virus vaccine: a randomised, double-blind, placebo-controlled, phase 1 clinical trial.

Background: The safety and immunogenicity of a highly attenuated recombinant vesicular stomatitis virus (rVSV) expressing HIV-1 gag (rVSVN4CT1-HIV-1gag1) was shown in previous phase 1 clinical studies. An rVSV vector expressing Ebola virus glycoprotein (EBOV-GP) in place of HIV-1 gag (rVSVN4CT1-EBOVGP1) showed single-dose protection from lethal challenge with low passage Ebola virus in non-human primates. We aimed to evaluate the safety and immunogenicity of the rVSVN4CT1-EBOVGP1 vaccine in healthy adults.

Treatment with milk fat globule epidermal growth factor-factor 8 (MFG-E8) reduces inflammation and lung injury in neonatal sepsis.

Background: Sepsis remains one of the leading causes of infant death worldwide. It is characterized by uncontrolled inflammatory responses due to proven bacterial infection. Despite improvement in supportive care and the availability of effective antibiotics, no specific therapy targeting the dysregulated inflammatory response is available for neonatal sepsis.

Targeted Fcγ Receptor (FcγR)-mediated Clearance by a Biparatopic Bispecific Antibody.

Soluble ligands have commonly been targeted by antibody therapeutics for cancers and other diseases. Although monoclonal antibodies targeting such ligands can block their interactions with their cognate receptors, they can also significantly increase the half-life of their ligands by FcRn-mediated antibody recycling, thereby evading ligand renal clearance and requiring increasingly high antibody doses to neutralize the increasing pool of target. To overcome this issue, we generated a bispecific/biparatopic antibody (BiSAb) that targets two different epitopes on IL-6 to block IL-6-mediated signaling.

Deficiency in milk fat globule-epidermal growth factor-factor 8 exacerbates organ injury and mortality in neonatal sepsis.

Introduction: Neonatal sepsis is a systemic inflammation occurring in neonates because of a proven infection within the first 28days of birth. It is the third leading cause of morbidity and mortality in the newborns. The mechanism(s) underlying the systemic inflammation in neonatal sepsis has not been completely understood.

SYNTHESIS AND STUDY OF HALOGENATED BENZYLAMIDES OF SOME ISOCYCLIC AND HETEROCYCLIC ACIDS AS POTENTIAL ANTICONVULSANTS.

A series of potential anticonvulsants have been synthesized. There are eight fluorobenzylamides and three chlorobenzylamides of isocyclic or heterocyclic acids. Two not halogenated benzylamides were also synthesized to compare the effect of halogenation.

Core stability exercise is as effective as task-oriented motor training in improving motor proficiency in children with developmental coordination disorder: a randomized controlled pilot study.

Objective: To compare the effectiveness of a core stability program with a task-oriented motor training program in improving motor proficiency in children with developmental coordination disorder (DCD).

Design: Randomized controlled pilot trial.

Setting: Outpatient unit in a hospital.

Study of CRTC2 pharmacology using antisense oligonuceotides.

The cAMP response element binding protein (CREB)-regulated transcriptional coactivator 2 (CRTC2) is a key component of the transcription complex regulating glucagon driven hepatic glucose production and previous evidence suggests that "inhibition" of CRTC2 improves glucose homeostasis in multiple rodent models of type 2 diabetes. Here we describe a process of identifying potential therapeutic antisense oligonucleotides (ASOs) directed against CRTC2. These ASOs were designed as locked nucleic acid (LNA) gapmers and a panel of approximately 400 sequences were first screened in vitro within both human and mouse liver cell lines.

Chemical modification study of antisense gapmers.

A series of insertion patterns for chemically modified nucleotides [2'-O-methyl (2'-OMe), 2'-fluoro (2'-F), methoxyethyl (MOE), locked nucleic acid (LNA), and G-Clamp] within antisense gapmers is studied in vitro and in vivo in the context of the glucocorticoid receptor. Correlation between lipid transfection and unassisted (gymnotic--using no transfection agent) in vitro assays is seen to be dependent on the chemical modification, with the in vivo results corresponding to the unassisted assay in vitro. While in vitro mRNA knockdown assays are typically reasonable predictors of in vivo results, G-Clamp modified antisense oligonucleotides have poor in vivo mRNA knockdown as compared to transfected cell based assays.

Targeting hyperphosphorylated tau with sodium selenate suppresses seizures in rodent models.

Tau hyperphosphorylation has been implicated in the pathogenesis of a variety of forms of human epilepsy. Here we investigated whether treatment with sodium selenate, a drug which reduces pathological hyperphosphorylated tau by enhancement of PP2A activity, would inhibit seizures in rodent models. In vitro, sodium selenate reduced tau phosphorylation in human neuroblastoma cells and reversed the increase in tau phosphorylation induced by the PP2A inhibitor, okadaic acid.

Correction of clubfoot deformity associated with Weber type I tibial hemimelia using the Ponseti method.

The clubfoot deformity associated with Weber type I tibial hemimelia, a rare congenital disorder, is rigid and difficult to correct. Surgeons have utilized a variety of treatment methods. Since the 1960s, some adopted the Syme amputation to produce a weightbearing lower limb.

Identification of small-molecule inhibitors of the JIP-JNK interaction.

JNK1 (c-Jun N-terminal kinase 1) plays a crucial role in the regulation of obesity-induced insulin resistance and is implicated in the pathology of Type 2 diabetes. Its partner, JIP1 (JNK-interacting protein 1), serves a scaffolding function that facilitates JNK1 activation by MKK4 [MAPK (mitogen-activated protein kinase) kinase 4] and MKK7 (MAPK kinase 7). For example, reduced insulin resistance and JNK activation are observed in JIP1-deficient mice.

Effects of pH and polyanions on the thermal stability of fibroblast growth factor 20.

Fibroblast growth factor 20 (FGF20) is a member of the FGF family with potential for use in several different therapeutic categories. In this work, we provide the first structural characterization of FGF20 using a wide variety of approaches. Like other members of the FGF family, FGF20 appears to possess a beta-trefoil structure.

Glutathione depletion renders rat hepatocytes sensitive to nitric oxide donor-mediated toxicity.

Nitric oxide (NO) can be either cytoprotective or cytotoxic in hepatocytes, depending on conditions within the cell. We hypothesized that redox status is a determinant of NO effects on cell viability. To cause the disturbance of redox homeostasis in the hepatocytes, cells were treated with the following glutathione (GSH) depleting agents: (1) chronic depletion by 18 hours pretreatment with buthionine sulfoximine (BSO), which depletes GSH by blocking its biosynthesis; and (2) acute depletion by 1 hour pretreatment with diethyl maleate (DEM), which conjugates GSH by the GSH-S-transferase catalyzed reaction.