Phenylthiazole Antibacterial Agents Targeting Cell Wall Synthesis Exhibit Potent Activity in Vitro and in Vivo against Vancomycin-Resistant Enterococci.

The emergence of antibiotic-resistant bacterial species, such as vancomycin-resistant enterococci (VRE), necessitates the development of new antimicrobials. Here, we investigate the spectrum of antibacterial activity of three phenylthiazole-substituted aminoguanidines. These compounds possess potent activity against VRE, inhibiting growth of clinical isolates at concentrations as low as 0.

Aryl-alkyl-lysines: Membrane-Active Fungicides That Act against Biofilms of Candida albicans.

Mortality due to pathogenic fungi has been exacerbated by the rapid development of resistance to frontline antifungal drugs. Fungicidal compounds with novel mechanisms of action are urgently needed. Aryl-alkyl-lysines, which are membrane-active small molecules, were earlier shown to be broad-spectrum antibacterial agents with potency in vitro and in vivo.

Long Term Outcomes of Kangaroo Mother Care in Very Low Birth Weight Infants.

Introduction: Kangaroo Mother Care (KMC) has been gaining acceptance as an effective alternative to incubator based Conventional Medical Care (CMC) in preterm or Low Birth Weight (LBW) infants especially in resource scarce developing countries.

Aim: To report and analyse the long-term effects of KMC for relatively stable Very Low Birth Weight (VLBW) infants on nutritional indicators and feeding conditions at 6-12 months of corrected age.

Materials And Methods: This randomized controlled trial was done at a Level III Neonatal Intensive Care Unit (NICU) of a teaching institution in southern India.

JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche.

This corrects the article DOI: 10.1038/mp.2016.

Repurposing Approach Identifies Auranofin with Broad Spectrum Antifungal Activity That Targets Mia40-Erv1 Pathway.

Current antifungal therapies have limited effectiveness in treating invasive fungal infections. Furthermore, the development of new antifungal is currently unable to keep pace with the urgent demand for safe and effective new drugs. Auranofin, an FDA-approved drug for the treatment of rheumatoid arthritis, inhibits growth of a diverse array of clinical isolates of fungi and represents a new antifungal agent with a previously unexploited mechanism of action.

Targeting biofilms and persisters of ESKAPE pathogens with P14KanS, a kanamycin peptide conjugate.

Background: The worldwide emergence of antibiotic resistance represents a serious medical threat. The ability of these resistant pathogens to form biofilms that are highly tolerant to antibiotics further aggravates the situation and leads to recurring infections. Thus, new therapeutic approaches that adopt novel mechanisms of action are urgently needed.

Phenylthiazole antibiotics: A metabolism-guided approach to overcome short duration of action.

Antibacterial resistance is a pressing global health challenge that necessitates the development of new therapeutic agents. Phenylthiazole antibacterial agents have been extensively studied, by our group, as a potential novel class of antibiotics to circumvent the scourge of antibacterial resistance. Previously, the phenylthiazole lead compound 1 was shown to possess potent activity against clinical isolates of methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA).

JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche.

Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region.

Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells.

Background: Ebselen, an organoselenium compound and a clinically safe molecule has been reported to possess potent antifungal activity, but its antifungal mechanism of action and in vivo antifungal activity remain unclear.

Methods: The antifungal effect of ebselen was tested against Candida albicans, C. glabrata, C.

An unusual presentation of arteriovenous malformation as an erosive midfoot lesion.

Erosive bony lesions are radiographic findings where localized bone resorption and cortical line breakage occurs. One less common cause of bone erosions is arteriovenous malformations (AVMs). This should always be included in the differentials for foot pain.

Urgent referral for suspected CNS cancer: which clinical features are associated with a positive predictive value of 3 % or more?

Background: Urgent referral for suspected central nervous system (CNS) cancer is recommended, but little analysis of the referral criteria diagnostic performance has been conducted. New 2015 NICE guidance recommends direct brain imaging for patients with symptoms with positive predictive values (PPV) of 3 %, but further guidance is needed.

Methods: A 12-month retrospective evaluation of 393 patients referred under previous 2005 NICE 2-week rule criteria was conducted.

Targeting Multidrug-resistant Staphylococci with an anti-rpoA Peptide Nucleic Acid Conjugated to the HIV-1 TAT Cell Penetrating Peptide.

Staphylococcus aureus infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibiotics. Due to their unique mode of action, peptide nucleic acids are novel alternatives to traditional antibiotics to tackle the issue of bacterial multidrug resistance. In this study, we designed a peptide nucleic acid covalently conjugated to the HIV-TAT cell penetrating peptide (GRKKKRRQRRRYK) in order to target the RNA polymerase α subunit gene (rpoA) required for bacterial genes transcription.

Antitumor activity of LSD1 inhibitors in lung cancer.

Epigenetic machinery have become a major focus for new targeted cancer therapies. Our previous report described the discovery and biological activity of a potent, selective, orally bioavailable, irreversible inhibitor of Lysine Demethylase 1 (LSD1), GSK2879552. A proliferation screen of cell lines representing a number of tumor types indicated that small cell lung carcinoma (SCLC) was sensitive to LSD1 inhibition.

A 47 Years Lady with Intrathoracic Lipoma.

A case of a 47 years old female who presented to Mymensingh Medical College Hospital, Medicine Unit-5, complaining of severe dyspnea and occasional leg swelling. Chest X-ray, USG of chest and chest CT scan revealed a right sided giant intrathoracic mass extending across the posterior mediastinum into the left chest cavity. CT guided FNAC of right lung revealed lipoma.

An unusual case of lipoma arborescens.

Introduction Lipoma arborescens is a rare condition of the synovial lining. It is particularly uncommon in the bicipitoradial bursae of the elbow. Case Report A 68-year-old woman presented with a 5-month history of anterior elbow pain and swelling causing discomfort.

Second-Generation Phenylthiazole Antibiotics with Enhanced Pharmacokinetic Properties.

A series of second-generation analogues for 2-(1-(2-(4-butylphenyl)-4-methylthiazol-5-yl)ethylidene)aminoguanidine (1) have been synthesized and tested against methicillin-resistant Staphylococcus aureus (MRSA). The compounds were designed with the objective of improving pharmacokinetic properties. This main aim has been accomplished by replacing the rapidly hydrolyzable Schiff-base moiety of first-generation members with a cyclic, unhydrolyzable pyrimidine ring.

Limb salvage talectomy for 3C Gustilo-Anderson fracture.

Foot fractures vary in severity with complex midfoot fractures having poor morbidity rates and high amputation rates. Complex midfoot fractures are rarely reported since they are uncommon and only treated in specialist centres. Given the important role of the midfoot in foot function, reconstruction is preferable.

Far lateral approach: Is condylar resection required?

Background: We report our experience with the far lateral approach (FLA) and its modifications in the surgical resection of tumors of craniocervical junction (CCJ).

Materials And Methodology: We retrospectively reviewed data of 36 patients with CCJ lesions who underwent surgical excision. Data are presented as frequency/percentages.

Structure-Based Design of a Novel SMYD3 Inhibitor that Bridges the SAM-and MEKK2-Binding Pockets.

SMYD3 is a lysine methyltransferase overexpressed in colorectal, breast, prostate, and hepatocellular tumors, and has been implicated as an oncogene in human malignancies. Methylation of MEKK2 by SMYD3 is important for regulation of the MEK/ERK pathway, suggesting the possibility of selectively targeting SMYD3 in RAS-driven cancers. Structural and kinetic characterization of SMYD3 was undertaken leading to a co-crystal structure of SMYD3 with a MEKK2-peptide substrate bound, and the observation that SMYD3 follows a partially processive mechanism.

Antibacterial activity and mechanism of action of auranofin against multi-drug resistant bacterial pathogens.

Traditional methods employed to discover new antibiotics are both a time-consuming and financially-taxing venture. This has led researchers to mine existing libraries of clinical molecules in order to repurpose old drugs for new applications (as antimicrobials). Such an effort led to the discovery of auranofin, a drug initially approved as an anti-rheumatic agent, which also possesses potent antibacterial activity in a clinically achievable range.

Evaluation of the surface roughness of three heat-cured acrylic denture base resins with different conventional lathe polishing techniques: A comparative study.

Purpose: Surface roughness promotes adhesion and colonization of denture plaque. Therefore, it is important to know the effects of polishing and finishing on the surface roughness of various acrylic resin materials.

Objectives: To evaluate and compare the effects of different conventional lathe polishing techniques on heat cured acrylic resins in producing surface roughness.

Repurposing auranofin for the treatment of cutaneous staphylococcal infections.

The scourge of multidrug-resistant bacterial infections necessitates the urgent development of novel antimicrobials to address this public health challenge. Drug repurposing is a proven strategy to discover new antimicrobial agents; given that these agents have undergone extensive toxicological and pharmacological analysis, repurposing is an effective method to reduce the time, cost and risk associated with traditional antibiotic innovation. In this study, the in vitro and in vivo antibacterial activities of an antirheumatic drug, auranofin, was investigated against multidrug-resistant Staphylococcus aureus.

Impact of different cell penetrating peptides on the efficacy of antisense therapeutics for targeting intracellular pathogens.

There is a pressing need for novel and innovative therapeutic strategies to address infections caused by intracellular pathogens. Peptide nucleic acids (PNAs) present a novel method to target intracellular pathogens due to their unique mechanism of action and their ability to be conjugated to cell penetrating peptides (CPP) to overcome challenging delivery barriers. In this study, we targeted the RNA polymerase α subunit (rpoA) using a PNA that was covalently conjugated to five different CPPs.

Waterpipe Tobacco Smoking among Arab Youth; a Cross-Country Study.

Objective: Waterpipe tobacco smoking (WTS) is considered a global epidemic that is spreading among youth. Our analysis was conducted to compare the national baseline prevalence rate estimates of WTS among Arab boys and girls.

Design Setting And Participants: The Global Youth Tobacco Survey (GYTS) is a school-based survey using standardized self-administered questionnaires; it employs a two-stage cluster sampling technique to obtain a representative sample of youth (13-15 years of age).

Rapid Intravenous Rehydration Therapy in Children With Acute Gastroenteritis: A Systematic Review.

Background: Rapid intravenous (IV) rehydration is commonly used for the management of pediatric gastroenteritis in the emergency department. The current practice shows wide variation in the volume and rate of rapid IV hydration. The aim of this review was to assess the efficacy of rapid IV rehydration compared with standard method in children with gastroenteritis.