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The incidence and mortality of breast cancer (BC) have increased in recent years, and BC is the main cause of cancer-related death in women worldwide. One of the most significant clinical problems in the treatment of patients with BC is the development of therapeutic resistance. Therefore, elucidating the molecular mechanisms involved in drug resistance is critical. The therapeutic decision for the management of patients with BC is based not only on the assessment of prognostic factors but also on the evaluation of clinical and pathological parameters. Although this has been a successful approach, some patients relapse and/or eventually develop resistance to treatment. This review is focused on recent studies on the possible biological and molecular mechanisms involved in both response and resistance to treatment in BC. Additionally, emerging treatments that seek to overcome resistance and reduce side effects are also described. A greater understanding of the mechanisms of action of treatments used in BC might contribute not only to the enhancement of our understanding of the mechanisms involved in the development of resistance but also to the optimization of the existing treatment regimens.

Cancer is one of the leading causes of death worldwide. Despite improvement in existing treatment modalities and addition of new anticancer drugs in the cancer clinic, cancer associated mortalities are continuously increasing. It is therefore, necessary to explore alternative treatment options to reduce the burden of cancer. In recent years, there is growing concern toward the use of natural products for treating cancer because of their ability to target multiple signaling molecules. α-solanine is a glycolalkaloid mainly present in potato tuber and Nightshade family plants. It possesses anti-pyretic, anti-diabetic, anti-allergic, anti-inflammatory and antibiotic activities. In recent years, α-solanine has been explored for its anticancer activity and showed promising results. Among all sources, potato peel contains adequate concentration of α-solanine. Every year, a large volume of potato peel is produced as a waste or sold at low cost. So α-solanine can be proved as an effective and cheap source for cancer therapy. The aim of this review is to summarize the recent data on anticancer activity of α-solanine and discuss it as a potential lead for cancer therapy.

With the rising prevalence of type 2 diabetes (T2D), there is a substantial interest in novel, glucose-lowering drugs that may complement existing treatment options. Imeglimin is an oral antidiabetic agent currently in clinical development.This review is based on a literature search using PubMed and Embase including all published manuscripts and presentations concerning imeglimin. Supplementary information was retrieved from the manufacturer's official webpage. Preclinical and clinical data are summarized with a focus on mechanisms of action as well as clinical efficacy and safety in T2D.Imeglimin's mode of action seems to be improved mitochondrial function in pancreatic beta cells leading to improved insulin secretion and lowering of plasma glucose levels. In clinical trials of up to 24 weeks, imeglimin in doses of 1,000-1,500 mg twice daily conferred modest reductions in glycates hemoglobin A1c of 6-11 mmol/mol (0.5-1.0%) (placebo-adjusted) as a monotherapy and 7 mmol/mol (0.6%) as an add-on therapy to metformin or sitagliptin in patients with T2D. Reported adverse effects were mainly gastrointestinal discomfort. The position of imeglimin among other pharmacotherapies in the treatment of T2D will be determined based on future studies more clearly outlining the safety and long-term cardiovascular effects.AUC: area under the curve; BID: twice daily; DPP-4: dipeptidyl peptidase 4; GLP-1R: glucagon-like peptide-1 receptor; HbA1c: glycated hemoglobin A1c; HFHSD: high-fat high-sucrose diet; OAD: oral antidiabetic; OD: once daily; OGTT: oral glucose tolerance test; PPAR-γ: peroxisome proliferator-activated receptor gamma; PTP: permeability transition pore; SGLT-2: sodium-glucose transport protein 2; STZ: streptozotocin; T2D: type 2 diabetes.

Targeting M. tuberculosis (Mtb) in latent form of infection is a major obstacle and big challenge in tuberculosis (TB) eradication by current chemotherapy. A better understanding of the physiology of Mtb and of the metabolic state of the bacillus during the dormancy, is a primary need in finding drug targets against non replicating persistent (NRP) form of the Mtb. Identification of potential drug targets against dormant state of Mtb is critically important to achieve the goal of complete eradication for shortening of anti-TB therapy. The metabolic processes functioning in dormant Mtb in providing cell viability and protecting Mtb from sterilization by the hostile environment can be explored as drug targets. This review discusses about the potential drug targets in dormant tubercle bacilli, anti-dormancy inhibitors and the strategies which can be pursued for maximizing success if these targets are exploited for killing the dormant bacilli. This has important implications as the currently available arsenal of drugs suffers from the demerit of achieving sterilizing killing of mycobacteria. This lacuna can be overcome if the proposed strategies for eliminating dormant bacteria are combined along with the existing treatment modalities for the extirpation of bacilli.

Methods for restoring endodontically treated teeth fall short of restoring the physiologic mechanical properties. Fracture of endodontically treated teeth is a common type of clinical failure. New treatment modalities or perfected versions of existing treatment concepts need to be tested to find a biomimetic solution. A novel method of restoring endodontically treated teeth is presented and compared in vitro with currently accepted restorative methods. Seventy-two extracted and endodontically treated maxillary premolar teeth were divided into six groups (n = 12) depending on restorative technique (Groups 1–6). Group 1: fiber-reinforced composite post (FRC), Group 2: direct layered short FRC post and core, Group 3: short fiber-reinforced obliquely layered composite restoration, Group 4: microhybrid composite restoration, Group 5: fiber-reinforced box, Group 6: control. Specimens were submitted to static fracture resistance test. Fracture thresholds and fracture patterns were evaluated. Group 6 exhi...

The development of family psychoeducation programs within low secure forensic mental health settings is limited. This paper describes the development, content, and structure of a family psychoeducation program piloted within a low secure forensic mental health setting. Additionally, the feasibility, acceptability, and resource implications are evaluated. The evaluation is descriptive in nature and based on broad feedback gathered from the five families and individuals directly involved, in addition to the views from the wider clinical team about the usefulness of the program. The intervention was well received by families and staff. Overall, the results suggest that family-based interventions in low secure settings can be developed from existing treatment being used in generic and forensic mental health settings. Research is now needed to assess the impact of the Family Psycho-Education Programme for Low Secure Settings (F-PEPSS) intervention on participants.

Introduction: The success of the first enzyme replacement therapy (ERT) for a lysosomal storage disease (LSD) and the regulatory and commercial incentives provided by authorities for orphan and rare diseases has spawned a massive interest for developing drugs for these intriguing but devastating genetic disorders. The potential for new drugs in this arena is vast, as not only a high number of LSDs have no available therapy, but also alternative therapeutic approaches for diseases with existing treatment are much needed as a number of challenges facing the existing therapies have become very obvious. A significant unmet medical need is therefore apparent for most, if not all of the LSDs and the development of new therapies based on the increasing knowledge of the pathophysiological mechanisms involved in these devastating diseases is therefore anticipated with great interest from all stakeholders. Areas covered: The reader will be introduced to the intricate biological processes involved in lysosomal regul...

A growing population of older adults receive treatment for depression but remain symptomatic. We report on a feasibility pilot study of an intervention (ACTIVATE) to improve depression care by encouraging the older person to take a step to intensify the existing treatment. Older adults (N = 43) receiving home-meal service and in depression treatment, but still symptomatic, participated in the ACTIVATE intervention. Assessments were conducted to evaluate change in treatment. Many (66.6%) participants took a step to change their treatment; the rate (88.2%) was higher among individuals with major depression. ACTIVATE may be a useful social work intervention to improve depression care.

Numerous researchers have identified a gap between empirically based findings on alcohol and other drug (AOD) treatment interventions and their utilization within clinical practice. Although there are various reasons for this lack of dissemination and implementation of proven practices, it is important to provide front-line clinicians with a user-friendly and measurable tool that evaluates and monitors clients’ progress during treatment. Because many AOD treatment facilities include some form of 12-step group attendance, particularly Alcoholics Anonymous (AA), the natural fit of the transtheoretical stages of change model (Prochaska & DiClemente, 1986) would seem a viable option for connecting research and practice within existing treatment programs. We propose a plan for social work clinicians working in the AOD treatment field to integrate the transtheoretical stages of change model into the process of monitoring clients who attend and work the12 Steps of AA. While the stages of change (SOC) model and the 12 Steps of AA (Alcoholics Anonymous, 1976) seem to be complementary, specific connections are not found in the literature. Connecting SOC and 12 Steps can assist treatment providers with client assessment, case formulation, treatment planning, and treatment implementation, along with evaluating and monitoring the client’s SOC process and 12 Step involvement.

The integration of brief alcohol treatment into an array of existing treatment services has been a challenge for clinical administrators despite the mounting evidence supporting brief treatment approaches. The present study examines the utility of a brief alcohol treatment program through an evaluation of client characteristics, use of program services, and preliminary program outcomes. Subjects were 256 clients receiving a Drinking Check-Up (DCU) program within a large, for-profit, private-practice-model, behavioral health services clinic. A process and outcome evaluation was conducted that included: (1) A detailed description of all clients enrolled in the DCU program; (2) A description of client utilization of DCU and other program services; and (3) A preliminary outcome evaluation of a subset of DCU participants. Analyses revealed nearly all (98%) clients who attended an initial screening/assessment session also attended a feedback/treatment planning session with about 59% attending at least ...

In 1998, responding to national and regional epidemiological data indicating that methamphetamine (MA) abuse was a growing problem in the United States, the Center for Substance Abuse Treatment (CSAT) initiated a multisite MA treatment study. Through a collaborative approach among CSAT, seven treatment sites, and a coordinating center, the study compares the clinical and cost effectiveness of a manualized, cognitive-behavioral outpatient treatment developed by the Matrix Center in Los Angeles to the treatment approaches currently employed by the treatment sites. The study also explores technology transfer issues associated with integrating the Matrix approach within existing treatment settings. CSAT's approach to the initiation and management of this type of study is discussed.

The year 1988 saw the publication of the influential first AIDS and Drug Misuse report from the Advisory Council on the Misuse of Drugs (ACMD, 1988) in the UK. Most of the policy documents and developments of practice in the intervening years can be seen as merely following through on the recommendations from this seminal 1988 report. Ten years on, it is appropriate to take stock of the situation and to describe some of the successes, reflect on the failures, and speculate on possible new areas of development in the harm reduction field. This paper comprises four parts. Firstly, what was new about the health risk facing the broader population of drug injectors—and how did this lead lo the public health approach that was adopted to dealing with the problems of HIV amongst injecting drug misusers? Secondly, an examination is required as to how concerns about HIV transmission have brought a new focus to the work of existing treatment services, as well as being the birthright of the new services established i...

This article addresses the need for mental health professionals to be alert to the specific psychological and social stressors affecting a large group of survivors of the ongoing AIDS epidemic: HIV-negative gay men. The difficult obstacles to surviving often release severe emotional reactions that at their worst can lead to self-destructive behaviors that put men at risk for contracting HIV. A protocol that integrates group work into existing treatment is described that helps being the delivery services to this often overlooked, traumatized population.

This article describes the addition of a Family Reunification Program to Boys Republic's existing treatment program. Families are invited to live in an apartment located at the institution and to participate in family therapy sessions.

Although primary hypochondriasis is a distressing condition, existing treatment is unsatisfactory and prognosis is poor. Understanding of the condition and hence development of satisfactory treatment is likely to be furthered by investigation of the psychological processes which may be involved in the aetiology and maintenance of the condition. The Illness Questionnaire, based on a cognitive-behavioural formulation of hypochondriasis, was administered to cases of DSM-III hypochondriasis and to normal controls. Cases of hypochondriasis were found to differ significantly from normal subjects, having more frequent fears about their health, more abnormal beliefs about illness and more frequent illness related behaviours.

The method of treatment described in this article first establishes a physiological mandibular position and then maintains this functional position throughout treatment. (This may involve conventional banded orthodontic techniques or passive eruption.) This system was specifically designed for treating patients who have TMJ dysfunction. The author presents case histories illustrating the corrections of a number of TMJ problems involving different stages of dysfunction. This system provides the practitioner with an option that can be incorporated easily into existing treatment modalities with little additional cost to the practitioner or the patient. It also offers positioning and precision that are not always available in other systems.

Genetic trace metal disturbances can be at three levels. Trace metals play an important role in the metabolism of genetic macromolecules and the information transfer system. Deficiency or excess of trace metals caused either by dietary or genetic factors will affect the normal functioning of the whole organism. The roles of trace metals in carcinogenesis/mutagenesis and ageing are typical of this category. The second level of genetic trace metal disturbances affect the metabolic pathway of the trace metal itself. Biochemical derangement resulting from genetic defects cause aberrant metabolism of the element and thus disease symptoms. Diseases caused by abnormal metabolism of copper, zinc, iron, and molybdenum are discussed. Trace metal disturbances can also be the result of other genetic diseases. This aspect of genetic trace metal disturbances is least investigated. However, information should be important for improving the existing treatment protocol for the more common inborn errors of metabolism, such as phenylketonuria.