Mechanical biofilm disruption causes microbial and immunological shifts in periodontitis patients

AbstractPeriodontitis is characterized by subgingival biofilm dysbiosis, inflammation and tissue destruction. Current treatment involves mechanical biofilm disruption known as non-surgical periodontal therapy (NSPT). This study sought to characterise the impact of treatment on microbial diversity and overall community, and the parallel impact on host inflammation in the oral cavity. Fourty-two periodontitis patients were included in this study, with periodontal clinical parameters, subgingival plaque and saliva samples collected at baseline and 90 days after treatment. Salivary cytokines were quantified, and subgingival plaque was analysed using 16S rRNA sequencing. After treatment, there were marked health-associated alterations in microbial composition and diversity, including differential abundance of 42 genera and 61 species. These changes were accompanied by substantial clinical improvement (pockets ≥ 5 mm, 27.50% to 9.00%, p < 0.001) and a decrease in salivary IL-1β (p < 0.001)—a putative marker of periodontal inflammation. Despite significant reductions in disease associated anaerobes, several genera (Fusobacterium, Prevotella, Tanenerella, Treponema) remained present and formed a distinct subnetwork associated with residual disease. Collectively, this study shows that current periodontal treatment results in partial restoration of a healthy microbial ecosystem, but features of biofilm dysbiosis and host inflammation remain in some patients, which were surprisingly independent of clinical response.

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The role of microbiome in rheumatoid arthritis treatment

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x19844632 ◽

2019 ◽

Vol 11 ◽

pp. 1759720X1984463 ◽

Cited By ~ 13

Author(s):

Rahul Bodkhe ◽

Baskar Balakrishnan ◽

Veena Taneja

Keyword(s):

Rheumatoid Arthritis ◽

Immune System ◽

Gut Microbiota ◽

Autoimmune Disorder ◽

Host Immune System ◽

Microbial Composition ◽

Drug Induced ◽

Partial Restoration ◽

Genetic And Environmental Factors ◽

The Impact

Rheumatoid arthritis (RA) is an autoimmune disorder with multifactorial etiology; both genetic and environmental factors are known to be involved in pathogenesis. Treatment with disease-modifying antirheumatic drugs (DMARDs) plays an essential role in controlling disease progression and symptoms. DMARDs have immunomodulatory properties and suppress immune response by interfering in various pro-inflammatory pathways. Recent evidence has shown that the gut microbiota directly and indirectly modulates the host immune system. RA has been associated with dysbiosis of the gut microbiota. Patients with RA treated with DMARDs show partial restoration of eubiotic gut microbiome. Hence, it is essential to understand the impact of DMARDs on the microbial composition and its consequent influences on the host immune system to identify novel therapies for RA. In this review, we discuss the importance of antirheumatic-drug-induced host microbiota modulations and possible probiotics that can generate eubiosis.

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The Current Understanding of and Treatment Paradigm for Newly-Diagnosed TP53-Mutated Acute Myeloid Leukemia

Hemato ◽

10.3390/hemato2040051 ◽

2021 ◽

Vol 2 (4) ◽

pp. 748-763

Author(s):

Rory M. Shallis ◽

Maximilian Stahl ◽

Jan Philipp Bewersdorf ◽

Amer M. Zeidan

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Residual Disease ◽

Disease Status ◽

Current Treatment ◽

Newly Diagnosed ◽

Hematopoietic Stem ◽

Treatment Paradigm ◽

The Impact ◽

Acute Myeloid

About 10% of newly diagnosed and 20–30% of therapy-related acute myeloid leukemia (AML) harbors a TP53 mutation (mTP53-AML). Unfortunately, this biological subset predicts one of the worst prognoses among patients with AML, specifically a median overall survival of about 7 months with fewer than 10% of patients eventually cured of disease. Although remission rates appear to be increased with venetoclax-based, less-intensive regimens when compared with contemporary, intensive chemotherapy (55–65% vs. 40%), survival appears to be no different between the two approaches. Attempts to discern whether or not the prognosis of mTP53-AML is universally poor have centered around the study of concurrent cytogenetic risk and predicted TP53 allelic state, measurable residual disease status and the impact of conditioning intensity for patients proceeding to allogeneic hematopoietic stem cell transplantation. We discuss these considerations in this review and offer the current treatment approach to TP53-mutated AML.

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MENTAL IMAGERY PRACTICE AS A THERAPY FOR NAMING IMPAIRMENTS: A PRELIMINARY STUDY

Acta Neuropsychologica ◽

10.5604/01.3001.0013.6197 ◽

2019 ◽

Vol 17 (3) ◽

pp. 311-327

Author(s):

Subhash Bhatnagar ◽

Bridget Patek ◽

Yasmeen Khan-Ansari ◽

Naveen Bansal ◽

Hugh Buckingham ◽

...

Keyword(s):

Mental Imagery ◽

Positive Impact ◽

Current Treatment ◽

Lexical Retrieval ◽

Exact Test ◽

Partial Restoration ◽

Word Finding ◽

Treatment Data ◽

Trial Treatment ◽

The Impact

Anomia remains one of the most recalcitrant linguistic disruptions in aphasia to treat. Developing successful interventions to address the word-finding deficits are complicated by the post-stroke symptom variability and inconsistent recovery patterns associated with anomia. Most of the current treatment methods, with a focus on specific compensating techniques and the repetitive practice of a limited set of items, have had variable success in naming treatment. However, it has not been possible to predict the gains in generalizing the learning beyond the stimuli used in practice or the controlled clinical setting. In this preliminary case study, we explore the value of a novel treatment concept, grounded in centuries of cognitive-perceptual exercises in mindfulness training. It incorporates the practice of mental imagery and focused attention to remedy the broken phonological assembly patterns found in word finding deficits. The aim of this study was to evaluate the potential effectiveness of practicing the repeated activation of mental imagery of concrete objects as a therapeutic tool for repairing disorders of lexical retrieval in a subject with chronic moderate to severe word-finding deficits. This trial treatment was used to assist a right-handed, 68-year old educated male with a two-and-a-half years post-onset chronic severe aphasia (anomic type) secondary to a left hemispheric infarct. Two five-week long training protocols involving common (typical) and uncommon (less typical) categories of pictured objects were used for treating anomia. The first trial involved the blocked presentation of stimuli; the second trial, undertaken a year after, included a random presentation of stimuli. It was found that the impact was manifested in three ways: (1) an improved verbal naming of the treated objects; (2) retention of therapeutic gains by a successful generalization to untreated similar lexical items; and (3) importantly, serendipitous gains in the ability to concurrently write the names of the pictured objects. The post-treatment data on all blocked lexical trials, and some random lexical trials, were found to be significant on the Fisher’s exact test. The use of the visual mental imagery-based therapy had a positive impact on the partial restoration of the subject’s naming.

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Curcumin-containing Silver Nanoparticles prevent carbon tetrachlorideinduced hepatotoxicity in mice

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666201211100830 ◽

2020 ◽

Vol 23 ◽

Author(s):

Hossam Ebaid ◽

Mohamed Habila ◽

Iftekhar Hassan ◽

Jameel Al-Tamimi ◽

Mohamed S. Omar ◽

...

Keyword(s):

Dna Damage ◽

Silver Nanoparticles ◽

Nuclear Dna ◽

Liquid Paraffin ◽

Tail Length ◽

Hepatic Tissue ◽

Tissue Destruction ◽

Group 2 ◽

The Impact

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

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MRD-Based Therapeutic Decisions in Genetically Defined Subsets of Adolescents and Young Adult Philadelphia-Negative ALL

Cancers ◽

10.3390/cancers13092108 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2108

Author(s):

Manuela Tosi ◽

Orietta Spinelli ◽

Matteo Leoncin ◽

Roberta Cavagna ◽

Chiara Pavoni ◽

...

Keyword(s):

Residual Disease ◽

Lymphoblastic Leukemia ◽

Survival Rates ◽

Philadelphia Chromosome ◽

Current Treatment ◽

New Drugs ◽

Term Survival ◽

Therapeutic Decisions ◽

Key Factor ◽

Combined Strategy

In many clinical studies published over the past 20 years, adolescents and young adults (AYA) with Philadelphia chromosome negative acute lymphoblastic leukemia (Ph− ALL) were considered as a rather homogeneous clinico-prognostic group of patients suitable to receive intensive pediatric-like regimens with an improved outcome compared with the use of traditional adult ALL protocols. The AYA group was defined in most studies by an age range of 18–40 years, with some exceptions (up to 45 years). The experience collected in pediatric ALL with the study of post-induction minimal residual disease (MRD) was rapidly duplicated in AYA ALL, making MRD a widely accepted key factor for risk stratification and risk-oriented therapy with or without allogeneic stem cell transplantation and experimental new drugs for patients with MRD detectable after highly intensive chemotherapy. This combined strategy has resulted in long-term survival rates of AYA patients of 60–80%. The present review examines the evidence for MRD-guided therapies in AYA’s Ph− ALL, provides a critical appraisal of current treatment pitfalls and illustrates the ways of achieving further therapeutic improvement according to the massive knowledge recently generated in the field of ALL biology and MRD/risk/subset-specific therapy

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Boosting Immunity against Multiple Myeloma

Cancers ◽

10.3390/cancers13061221 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1221

Author(s):

Raquel Lopes ◽

Bruna Velosa Ferreira ◽

Joana Caetano ◽

Filipa Barahona ◽

Emilie Arnault Carneiro ◽

...

Keyword(s):

Multiple Myeloma ◽

Residual Disease ◽

Proteasome Inhibitors ◽

Treatment Strategies ◽

Complete Response ◽

Drug Conjugates ◽

Incurable Disease ◽

Car T ◽

Patient’S Outcome ◽

The Impact

Despite the improvement of patient’s outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody–drug conjugates or bispecific antibodies broadened the possibility of improving patients’ survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residual disease (MRD)-negative status. In this sense, approaches that target not only myeloma cells but also the surrounding microenvironment are promising strategies to achieve a sustained MRD negativity with prolonged survival. This review provides an overview of current and future strategies used for immunomodulation of MM focusing on the impact on bone marrow (BM) immunome.

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Cisplatin +/− rucaparib after preoperative chemotherapy in patients with triple-negative or BRCA mutated breast cancer

npj Breast Cancer ◽

10.1038/s41523-021-00240-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Maitri Kalra ◽

Yan Tong ◽

David R. Jones ◽

Tom Walsh ◽

Michael A. Danso ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Neoadjuvant Therapy ◽

Triple Negative ◽

Residual Disease ◽

Disease Free Survival ◽

Parp Inhibition ◽

High Risk Population ◽

Risk Population ◽

The Impact

AbstractPatients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.

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Cost-effectiveness of new MDR-TB regimens: study protocol for the TB-PRACTECAL economic evaluation substudy

BMJ Open ◽

10.1136/bmjopen-2019-036599 ◽

2020 ◽

Vol 10 (10) ◽

pp. e036599

Author(s):

Sedona Sweeney ◽

Gabriela Gomez ◽

Nichola Kitson ◽

Animesh Sinha ◽

Natalia Yatskevich ◽

...

Keyword(s):

Economic Evaluation ◽

Cost Effectiveness ◽

Best Practice ◽

Current Treatment ◽

Outcome Data ◽

London School ◽

Main Trial ◽

Ethical Approval ◽

Mdr Tb ◽

The Impact

IntroductionCurrent treatment regimens for multidrug-resistant tuberculosis (MDR-TB) are long, poorly tolerated and have poor outcomes. Furthermore, the costs of treating MDR-TB are much greater than those for treating drug-susceptible TB, both for health service and patient-incurred costs. Urgent action is needed to identify short, effective, tolerable and cheaper treatments for people with both quinolone-susceptible and quinolone-resistant MDR-TB. We present the protocol for an economic evaluation (PRACTECAL-EE substudy) alongside an ongoing clinical trial (TB-PRACTECAL) aiming to assess the costs to patients and providers of new regimens, as well as their cost-effectiveness and impact on participant poverty levels. This substudy is based on data from the three countries participating in the main trial.Methods and analysisPrimary cost data will be collected from the provider and patient perspectives, following economic best practice. We will estimate the probability that new MDR-TB regimens containing bedaquiline, pretomanid and linezolid are cost-effective from a societal perspective as compared with the standard of care for MDR-TB patients in Uzbekistan, South Africa and Belarus. Analysis uses a Markov model populated with primary cost and outcome data collected at each study site. We will also estimate the impact of new regimens on prevalence of catastrophic patient costs due to TB.Ethics and disseminationEthical approval has been obtained from the London School of Hygiene & Tropical Medicine and Médecins Sans Frontières. Local ethical approval will be sought in each study site. The results of the economic evaluation will be shared with the country health authorities and published in a peer-reviewed journal.Trial registration numberClinicalTrials.gov Registry (NCT04207112); Pre-results.

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Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽

10.3390/biomedicines9020145 ◽

2021 ◽

Vol 9 (2) ◽

pp. 145

Author(s):

Julio Plaza-Díaz ◽

Patricio Solis-Urra ◽

Jerónimo Aragón-Vela ◽

Fernando Rodríguez-Rodríguez ◽

Jorge Olivares-Arancibia ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Liver Steatosis ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Current Treatment ◽

Immune Defense ◽

Alcoholic Fatty Liver ◽

The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

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