Development of -(4-(1-Imidazol-1-yl)phenyl)-4-chlorobenzenesulfonamide, a Novel Potent Inhibitor of β-Catenin with Enhanced Antitumor Activity and Metabolic Stability.

The potential as a cancer therapeutic target of the recently reported hotspot binding region close to Lys508 of the β-catenin armadillo repeat domain was not exhaustively explored. In order to get more insight, we synthesized novel -(heterocyclylphenyl)benzenesulfonamides -. The new compounds significantly inhibited Wnt-dependent transcription as well as SW480 and HCT116 cancer cell proliferation.

Novel -(Heterocyclylphenyl)benzensulfonamide Sharing an Unreported Binding Site with T-Cell Factor 4 at the β-Catenin Armadillo Repeats Domain as an Anticancer Agent.

Despite intensive efforts, no inhibitors of the Wnt/β-catenin signaling pathway have been approved so far for the clinical treatment of cancer. We synthesized novel -(heterocyclylphenyl)benzenesulfonamides as β-catenin inhibitors. Compounds - showed strong inhibition of the luciferase activity.

Discovery of novel human lactate dehydrogenase inhibitors: Structure-based virtual screening studies and biological assessment.

Most cancer cells switch their metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis to generate ATP and precursors for the biosynthesis of key macromolecules. The aerobic conversion of pyruvate to lactate, coupled to oxidation of the nicotinamide cofactor, is a primary hallmark of cancer and is catalyzed by lactate dehydrogenase (LDH), a central effector of this pathological reprogrammed metabolism. Hence, inhibition of LDH is a potential new promising therapeutic approach for cancer.

Prevalence of burnout syndrome among Italian volunteers of the Red Cross: a cross-sectional study.

Burnout syndrome (BOS) is a work-related constellation of symptoms characterized by emotional exhaustion, depersonalization, and personal accomplishment. A cross-sectional survey was performed to study the prevalence of BOS among a randomly selected sample of 280 Italian Red Cross volunteers. A socio-demographic questionnaire and the Maslach Burnout Inventory (MBI)-HSS were used to collect data.

Comparison of Different Swabs for Sampling Inorganic Gunshot Residue from Gunshot Wounds: Applicability and Reliability for the Determination of Firing Distance.

This study concentrates on samples of bare pork skin, with and without bristles, and dried bovine ribs shot with a semi-automatic pistol to find the best methodology and sampling surface in the search for inorganic gunshot residues (IGSR). Four quadrants of known surface areas were sampled at different distances from the bullet's hole with different swabs: tapes in graphite, Leukosilk® white tape, 3M® transparent tape, and a cotton swab to assess the technique able to collect the highest amounts of IGSR with the lowest contribution of the blank. The cotton swab wet in 10% HNO gave the best results.

Identifying optimal dosage regimes under safety constraints: An application to long term opioid treatment of chronic pain.

There is growing interest and investment in precision medicine as a means to provide the best possible health care. A treatment regime formalizes precision medicine as a sequence of decision rules, one per clinical intervention period, that specify if, when and how current treatment should be adjusted in response to a patient's evolving health status. It is standard to define a regime as optimal if, when applied to a population of interest, it maximizes the mean of some desirable clinical outcome, such as efficacy.

Safety and effectiveness of once-daily Hysingla extended-release tablets in patients with baseline depression or anxiety.

Aim: Long-term safety and effectiveness of a once-daily, single-entity, extended-release formulation of hydrocodone bitartrate (HYD) for the treatment of moderate to severe noncancer and nonneuropathic pain among patients with and without concurrent depression/anxiety at baseline.

Materials & Methods: Post hoc analysis.

Results: HYD demonstrated a safety profile consistent with μ-opioid agonists: Serious adverse events in 12% patients with depression/anxiety including four deaths; 6% without depression/anxiety including one death.

Use of immediate-release opioids as supplemental analgesia during management of moderate-to-severe chronic pain with buprenorphine transdermal system.

Background: The buprenorphine transdermal system (BTDS) is approved in the US for the management of chronic pain. Due to its high affinity for μ-opioid receptors with a slow dissociation profile, buprenorphine may potentially displace or prevent the binding of competing μ-opioid-receptor agonists, including immediate-release (IR) opioids, in a dose-dependent manner. Health care professionals may assume that the use of IR opioids for supplemental analgesia during BTDS therapy is not acceptable.

Evaluation of the Ototoxicity Potential of Once-Daily, Single-Entity Hydrocodone in Patients with Chronic Pain: Results of Two Phase-3 Clinical Studies.

Background: Use/misuse of the opioid combination hydrocodone-acetaminophen has been associated with permanent hearing loss. Although reports have been rare, this potential effect can have significant detrimental effect on patients' overall quality of life. To date, the ototoxic effect of hydrocodone alone has not been systematically investigated.

Hysingla® ER, a once-daily, single-entity hydrocodone with abuse-deterrent properties in treating chronic nonmalignant and nonneuropathic pain in patients with osteoarthritis.

Objectives: Osteoarthritis (OA)-related chronic pain is associated with physical and psychosocial impairment as well as poorer quality of life. There is limited literature on long-term opioid therapy in OA patients. This post hoc analysis of OA patients assessed the long-term safety and effectiveness of a once-daily, single-entity, extended-release formulation of hydrocodone (HYD) with abuse-deterrent properties for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which other treatment options are inadequate.

Safety of buprenorphine transdermal system in the management of pain in older adults.

Objectives: To evaluate whether buprenorphine transdermal system (BTDS; Butrans®) is an option for the treatment of chronic pain in older adults.

Methods: This retrospective analysis of 16 placebo- and active-controlled and uncontrolled studies (N = 6566) evaluated the safety and tolerability profile in patients exposed to BTDS and compared the safety profiles associated with BTDS treatment in older patients ≥ 65 years of age (65 to 98 years) and younger patients < 65 years of age (18 to 64 years). Safety analyses included adverse events (AEs), laboratory values, and electrocardiograms.

Effects of buprenorphine on QT intervals in healthy subjects: results of 2 randomized positive- and placebo-controlled trials.

Objectives: To study the effect of transdermal buprenorphine on QTc prolongation at dose levels of 10, 40, and 80 mcg/h, (BTDS 10, BTDS 40, BTDS 80).

Methods: Two randomized, placebo- and positive-controlled, parallel-group, dose-escalating clinical studies evaluated healthy adult subjects randomized to BTDS, placebo, or moxifloxacin in the first study; and to BTDS only, BTDS plus naltrexone, naltrexone alone at the same dose, placebo, or moxifloxacin in the second study. QT intervals were corrected for heart rate using data from each individual subject (QTcI).

Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain.

Objective: To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain.

Methods: This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily.

12-Month safety and effectiveness of once-daily hydrocodone tablets formulated with abuse-deterrent properties in patients with moderate to severe chronic pain.

Objective: To characterize the long-term safety and effectiveness of Hysingla™ ER, single-entity, once-daily, extended-release hydrocodone bitartrate tablets formulated with abuse-deterrent properties (HYD), offering a new treatment option for appropriate patients with chronic pain.

Design: An open-label study with a dose-titration period (up to 45 days) and a maintenance period (12 months).

Patients, Participants: A total of 922 patients with chronic nonmalignant and non-neuropathic moderate to severe pain received open-label HYD tablets 20-120 mg; 728 of these achieved a stabilized dose of HYD at the end of dose-titration and entered the maintenance period.

A multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of single-entity, once-daily hydrocodone tablets in patients with uncontrolled moderate to severe chronic low back pain.

Objectives: This multicenter, randomized, double-blind, placebo-controlled study with an enriched enrollment, randomized withdrawal design was conducted to evaluate the analgesic efficacy and safety of single-entity, once-daily hydrocodone 20 to 120 mg tablets (HYD) in opioid-naive and opioid-experienced patients with uncontrolled moderate to severe chronic low back pain (CLBP).

Research Design And Methods: The primary endpoint was week 12 pain intensity scores (11-point scale, 0 = no pain) using a mixed effect model with repeated measures incorporating a pattern mixture model framework. Responder analysis was a secondary endpoint.

A Subgroup Analysis Found no Diminished Response to Buprenorphine Transdermal System Treatment for Chronic Low Back Pain Patients Classified with Depression.

Background: Chronic pain (CP) patients with depression typically exhibit worse post-treatment outcomes than nondepressed CP patients. The cause is often assumed to reflect a differential response to treatment, neglecting other potential explanations, such as the continuation of differences in pretreatment outcomes. This post hoc analysis examines whether worse post-treatment outcomes for depressed patients with chronic low back pain (CLBP) are driven by reduced treatment efficacy.

Buprenorphine Transdermal System Improves Sleep Quality and Reduces Sleep Disturbance in Patients with Moderate-to-Severe Chronic Low Back Pain: Results from Two Randomized Controlled Trials.

Objective: To evaluate the impact of buprenorphine (Butrans®) transdermal System (BTDS) treatment on sleep outcomes for patients with moderate-to-severe chronic low back pain (CLBP).

Methods: Two enriched-enrollment, randomized-withdrawal, double-blind, controlled trials examined BTDS treatment for patients with moderate-to-severe CLBP. Trial I evaluated BTDS 10 and 20 mcg/hour against a placebo control among opioid-naïve patients.

Buprenorphine transdermal system compared with placebo reduces interference in functioning for chronic low back pain.

Objective: This study examines the efficacy of the buprenorphine transdermal system (BTDS) for reducing the interference of pain on physical and emotional functioning associated with chronic low back pain (CLBP).

Methods: A post-hoc analysis used data from a randomized, placebo-controlled, double-blind trial of patients with moderate-to-severe CLBP. The Brief Pain Inventory (BPI) measured pain interference at screening, following a run-in period, and during the 12-week double-blind treatment phase.

[Coffee consumption in depressive disorders: it's not one size fits all].

Caffeine is considered the world's most popular psychoactive substance. Its actions on the central nervous system, mainly mediated by antagonism of adenosine receptors and subsequent modulation of dopaminergic activity, would be particularly sought by depressed patients, as an attempt of self-medication. However, published data suggested that coffee consumption may worsen psychopathological conditions in mood disorders.

The impact of buprenorphine transdermal delivery system on activities of daily living among patients with chronic low back pain: an application of the international classification of functioning, disability and health.

Objectives: The buprenorphine transdermal delivery system (BTDS) is indicated for reduction of pain in moderate to severe chronic low back pain (CLBP), which can affect patients' ability to perform routine activities of daily living (ADLs). This post hoc analysis of clinical trial data examines the impact of BTDS treatment on CLBP patients' ability to perform ADLs that relate to functioning with low back pain.

Methods: Data are drawn from a multicenter, enriched enrollment, randomized, placebo-controlled, double-blind 12-week trial of BTDS for pain control among opioid-naive patients with moderate to severe CLBP.

Application site adverse events associated with the buprenorphine transdermal system: a pooled analysis.

Objective: To characterize the profile of application site reactions (ASRs) for patients treated with the buprenorphine transdermal system (BTDS) in chronic pain studies.

Methods: The incidences of ASRs during treatment with BTDS were examined using (a) integrated data from 16 controlled and uncontrolled Phase III chronic pain studies (N = 6566), (b) a subset of integrated data that focused on the double-blind phases of five enriched, placebo-controlled studies (n = 1806) and (c) data from an international postmarketing drug safety database. These data were compared with the ASR data reported in the full prescribing information of other transdermal patches marketed in the US.

Buprenorphine transdermal system and quality of life in opioid-experienced patients with chronic low back pain.

Objectives: To evaluate the impact of 12 weeks of treatment with Butrans® (buprenorphine) transdermal system (BTDS) on the health-related quality of life (HRQoL) for patients with chronic low back pain (CLBP), and the maintenance of effects over 52 weeks.

Research Design And Methods: A multicenter, enriched, double-blind (DB), randomized trial comparing BTDS 20 μg/h (BTDS 20) against 5 μg/h (BTDS 5) for treatment of opioid-experienced patients with moderate-to-severe CLBP, including a 52-week open-label (OL) extension phase.

Main Outcome Measures: QoL was measured with the SF-36v2 survey before and after an OL run-in period with BTDS 20, three times during the DB phase, and seven times over the extension phase.

A randomized, placebo-controlled study of the impact of the 7-day buprenorphine transdermal system on health-related quality of life in opioid-naïve patients with moderate-to-severe chronic low back pain.

Unlabelled: This study evaluated the impact of treatment with Buprenorphine Transdermal System (BTDS) on the health-related quality of life for patients with moderate-to-severe chronic low back pain (CLBP), and the correspondence between quality of life and pain. A multicenter, enriched, double-blind (DB), placebo-controlled, randomized trial evaluated BTDS 10 and 20 μg/hour for treatment of opioid-naïve patients with moderate-to-severe CLBP. The SF-36v2 survey, which measures 8 domains of quality of life, was administered at screening and following an open-label run-in period with BTDS and at weeks 4, 8, and 12 of the DB phase.

Outer membrane protein A (OmpA): a new player in shigella flexneri protrusion formation and inter-cellular spreading.

Outer membrane protein A (OmpA) is a multifaceted predominant outer membrane protein of Escherichia coli and other Enterobacteriaceae whose role in the pathogenesis of various bacterial infections has recently been recognized. Here, the role of OmpA on the virulence of Shigella flexneri has been investigated. An ompA mutant of wild-type S.

Antibacterial activity of various antibiotics against oral streptococci isolated in the oral cavity.

A total of 550 oral streptococci: 270 Streptococcus mitis, 110 Streptococcus sanguis, 90 Streptococcus anginosus, 50 Streptococcus mutans, 30 Streptococcus salivarius, were isolated from dental plaque and gengival crevices of patients and tested for their susceptibility to 12 β-lactam antibiotics and to 5 non-β-lactam antibiotics, using the microdiluition method. Overall, a reduced susceptibility to penicillin was recorded in 13.4% of cases.