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Inflammasome dysfunction may be responsible for underlying inflammatory diseases, which include renal and urological pathologies. Five inflammasomes have been described, including nucleotide-binding domain leucine-rich repeat (NLR), NL pyrin domain containing receptor 1(NLPR1), NLRP3, NLR and caspase recruitment domain containing receptor 4 (NLRC4), and the AIM2-like receptor. The purpose of this study was to review literature sources regarding how innate immunity and inflammasomes contribute to urologic disease and infection. A literature search of PubMed/MEDLINE, EMBASE and Google Scholar articles. Articles were selected for review if their content included (1) inflammasomes and (2) urology in the adult population. The initiation of specific cytokine cascades, which include IL-1β and IL-18, appear responsible for a repertoire of urologic pathologies. Inflammation mediates a wide range of uropathies (urologic disorders and infections) which are found in the bladder, prostate, or kidney and inflammasomes appear to be particularly responsible for urological and renal pathologies. Understanding the role of inflammasomes in urologic disorders can help improve treatment and overall quality of life in patients with these disorders.

Mounting evidence demonstrates that meditation can lower pain and emotional distress in adults, and more recently, in children. Children may benefit from meditation given its accessibility across a variety of settings (e.g., surgical preparation). Recent neuroimaging studies in adults suggest that meditation techniques are neurobiologically distinct from other forms of emotion regulation, such as distraction, that rely on prefrontal control mechanisms, which are underdeveloped in youth. Rather, meditation techniques may not rely on "top-down" prefrontal control and may therefore be utilized across the lifespan.We examined neural activation in children with cancer, a potentially distressing diagnosis. During neuroimaging, children viewed distress-inducing video clips while using martial arts-based meditation (focused attention, mindful acceptance) or non-meditation (distraction) emotion regulation techniques. In a third condition (control), participants passively viewed the video clip.We found that meditation techniques were associated with lower activation in default mode network (DMN) regions, including the medial frontal cortex, precuneus, and posterior cingulate cortex, compared to the control condition. Additionally, we found evidence that meditation techniques may be more effective for modulating DMN activity than distraction. There were no differences in self-reported distress ratings between conditions.Together, these findings suggest that martial arts-based meditation modulates negative self-referential processing associated with the DMN, and may have implications for the management of pediatric pain and negative emotion.

Rachelle Mendoza,1 Michael Silver,2,3 Alejandro R Zuretti,1,4 Manan Christian,4 Ballabh Das,5 Allen J Norin,5 Patrick Borgen,6 Jenny Libien,1,4 Martin H Bluth4 1Department of Pathology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA; 2School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, NY, USA; 3Department of Medicine, Maimonides Medical Center, Brooklyn, NY, USA; 4Department of Pathology, Maimonides Medical Center, Brooklyn, NY, USA; 5Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, USA; 6Department of Surgery, Maimonides Medical Center, Brooklyn, NY, USACorrespondence: Martin H BluthBlood Transfusion and Donor Services, Clinical Laboratories, Translational Research (Pathology), Maimonides Medical Center, 4802 10 th Avenue, Brooklyn, NY, 11219, USAEmail MBluth@maimonidesmed.orgBackground: We investigated the utility of an automated chemiluminescent SARS-CoV-2 IgG antibody assay platform in quantifying the amount of binding antibodies present in donated convalescent plasma.Methods: A total of 179 convalescent plasma units were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Beckman-Coulter chemiluminescent immunoassay (CLIA) platform. The equipment-derived numerical values (S/Co ratio) were recorded. Aliquots from the same units were subjected to enzyme-linked immunosorbent assay (ELISA) that detects IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 S1 protein. The relationship between ELISA titers and CLIA S/Co values was analyzed using linear regression and receiver operating characteristics (ROC) curve.Results: Twenty-one samples (11.7%) had S/Co values of less than 1.0 and were deemed negative for antibodies and convalescent plasma had S/Co values between > 1.0 and 5.0 (70/179, 39.1%). Fifteen units (8.4%) had negative ELISA titer. The majority of the units (95/179. 53.1%) had titers ≥ 1:1024. The sensitivities of ELISA to CLIA were comparable (90.5% vs 88.3%, respectively; p=0.18). There was positive linear correlation between CLIA S/Co values and ELISA IgG titer (Rho = 0.75; Spearman’s rank = 0.82, p-value = < 0.0001). The agreement between the two methods was fair, with a κ index of 0.2741. Using the ROC analysis, we identified a CLIA S/Co cutoff value of 8.2, which gives a sensitivity of 90% and a specificity of 82% in predicting a titer dilution of ≥ 1:1024.Conclusion: The utility of automated antibody detection systems can be extended from simply a screening method to a semi-quantitative and quantitative functional antibody analysis. CLIA S/Co values can be used to reliably estimate the ELISA antibody titer. Incorporation of chemiluminescent-based methods can provide rapid, cost-effective means of identifying anti-SARS-CoV-2 antibody titers in donated plasma for use in the treatment of COVID-19 infection.Keywords: COVID-19, ELISA, chemiluminescence, antibody, titers

Hilary A Marusak,1– 3 Allesandra S Iadipaolo,4 Cindy Cohen,5 Elimelech Goldberg,5,6 Jeffrey W Taub,6,7 Felicity WK Harper,3,7 Martin H Bluth,5,8 Christine A Rabinak1,2,4,9 1Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, USA; 2Merrill Palmer Skillman Institute, Wayne State University, Detroit, MI, USA; 3Population Studies and Disparities Research Program, Karmanos Cancer Institute, Detroit, MI, USA; 4Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA; 5Kids Kicking Cancer, Southfield, MI, USA; 6Department of Pediatrics, School of Medicine, Wayne State University, Detroit, MI, USA; 7Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA; 8Department of Pathology, School of Medicine, Wayne State University, Detroit, MI, USA; 9Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USACorrespondence: Hilary A Marusak Tel +1 313-577-1278Fax +1 313-577-6188Email hmarusak@med.wayne.eduObjective: Test whether a martial arts-based therapy, Kids Kicking Cancer (KKC), can reduce pain and emotional distress in children with cancer, other chronic health conditions (e.g., sickle cell), and healthy siblings.Methods: This study surveyed children’s pain and distress levels immediately before and after a 1-hr in-person KKC class. Eligible participants were enrolled in standard KKC classes, were diagnosed with a chronic health condition (e.g., cancer, sickle cell) or were the sibling of a child diagnosed and were between the ages of 5– 17 years (inclusive). Children reported on their pain and distress using Likert-style scales (Coloured Analog Scale and modified FACES scale, respectively). Friedman test was used to test for overall changes in pain and distress, and within subgroups. Age and sex effects were evaluated using Spearman’s rank-order correlation. Additional Yes/No questions were administered regarding KKC satisfaction and use of techniques.Results: Fifty-nine youth (19 cancer patients, 17 non-cancer patients, 23 siblings; 5– 17 yrs, 26 females) completed this study. Overall, there was a significant reduction in pain (p = 0.033) and emotional distress (p < 0.001) after a 1-hr class, with 50% and 89% of youth reporting a reduction in pain and distress, respectively. On average, pain levels remained within the mild/moderate range on average (i.e., pre vs. post levels; pre: M = 1.67, post: M = 1.33) and emotional distress went from mild/moderate to none/mild distress, on average (pre: M = 1.92, post: M = 1.08). Youth with higher pre-class pain and distress reported greater reductions (p = 0.001 and p < 0.001, respectively). The reduction in pain appeared to be most pronounced with cancer and non-cancer patients. In contrast, the reduction in distress appeared to be most pronounced among healthy siblings. However, overall, reductions in pain and distress did not significantly differ among subgroups (i.e., cancer patients, non-cancer patients, siblings), and change in pain and distress was not associated with age or sex. Ninety-six percent of youth would recommend KKC to others and 81% reported using KKC techniques (e.g., the Breath BrakeTM or other martial arts techniques) outside of class, such as at home.Conclusion: Results support the more widespread application of KKC as a psychosocial intervention for reducing pain and distress in various pediatric populations.Keywords: meditation, mindfulness, oncology, psychosocial, sickle cell, leukemia

Background/aim Anticancer peptide PNC-27 binds to HDM-2 protein on cancer cell membranes inducing the formation of cytotoxic transmembrane pores. Herein, we investigated HDM-2 membrane expression and the effect of PNC-27 treatment on human non-stem cell acute myelogenous leukemia cell lines: U937, acute monocytic leukemia; OCI-AML3, acute myelomonocytic leukemia and HL60, acute promyelocytic leukemia. Materials and methods We measured cell surface membrane expression of HDM-2 using flow cytometry. Cell viability was assessed using MTT assay while direct cytotoxicity was measured by lactate dehydrogenase (LDH) release and induction of apoptotic markers annexin V and caspase-3. Results HDM-2 is expressed at high levels in membranes of U937, OCI-AML3 and HL-60 cells. PNC-27 can bind to membrane HDM-2 to induce cell necrosis and LDH release within 4 h. Conclusion Targeting membrane HDM-2 can be a potential strategy to treat leukemia. PNC-27 targeting membrane HDM-2 demonstrated significant anti-leukemia activity in a variety of leukemic cell lines.

This exploratory study examined the impact of Heroes Circle, a martial arts-based curriculum on stress, emotional, and behavioral problems in elementary school children. While students completed classroom surveys at baseline, post-curriculum surveys were collected from teachers, students, and parents/guardians two and five months after COVID-19-related school shutdowns. Satisfaction with the curriculum was high among those who received the intervention. Children reported increased mindfulness and decreased stress over the school year. Most children (77%) were still using the program's techniques and reporting benefits five months later, including lower internalizing symptoms and COVID-19-related fears. These patterns were not observed at the control school.

Utilization of therapeutic plasma exchange in select patients with COVID‐19 microangiopathy may provide useful treatment by modulation of inflammatory cytokines and coagulation cascade to maintain homeostasis.

Objective Standard of care for opioid use disorder (OUD) includes medication and counseling. However, there is an unmet need for complementary approaches to treat OUD patients coping with pain; furthermore, few studies have probed neurobiological features of pain or its management during OUD treatment. This preliminary study examines neurobiological and behavioral effects of a virtual reality-based meditative intervention in patients undergoing methadone maintenance treatment (MMT). Design Prospective, non-blinded, single-arm, 12-week intervention with standardized assessments. Setting Academic research laboratory affiliated with an on-site MMT clinic. Methods Fifteen (11 female) MMT patients completed a virtual reality, therapist-guided meditative intervention that included breathing and relaxation exercisessessions were scheduled twice weekly. Assessments included functional magnetic resonance imaging (fMRI) of pain neuromatrix activation and connectivity (pre- and post-intervention), saliva cortisol and C-reactive protein (CRP) at baseline and weeks 4, 8 and 12; and self-reported pain and affective symptoms before and after each intervention session. Results After each intervention session (relative to pre-session), ratings of pain, opioid craving, anxiety and depression (but not anger) decreased. Saliva cortisol (but not CRP) levels decreased from pre- to post-session. From pre- to post-intervention fMRI assessments, pain task-related left postcentral gyrus (PCG) activation decreased. At baseline, PCG showed positive connectivity with other regions of the pain neuromatrix, but this pattern changed post-intervention. Conclusions These preliminary findings demonstrate feasibility, therapeutic promise, and brain basis of a meditative intervention for OUD patients undergoing MMT.

Neoplasms of the small intestine are rare in comparison with colorectal tumors. The most common tumor types arising in the small intestine are adenocarcinomas, well-differentiated neuroendocrine tumors, gastrointestinal stromal tumors, and lymphoma. Primary appendiceal neoplasms are rare and found in less than 2% of appendectomy specimens with an incidence of approximately 1.2 cases per 100,000 people per year in the United States. This article explores molecular diagnostics in the neoplasms of small intestine and appendix.

Diagnosis of hematologic malignancies have matured to encompass molecular as well as phenotypic characteristics. Cytogenetic abnormalities are considered common events in this regard. These abnormalities generally consist of structural chromosomal abnormalities or gene mutations, which often are integral to the pathogenesis and subsequent evolution of an individual malignancy. Improvements made in identifying and interpreting these molecular alterations have resulted in advances in the diagnosis, prognosis, monitoring, and therapy for cancer. As a consequence of the increasingly important role of molecular testing in hematologic malignancy management, this article presents an update on the importance and use of molecular tests, detailing the advantages and disadvantages of each test when applicable.

Virtually all the red blood cell and platelet antigen systems have been characterized at the molecular level. Highly reliable methods for red blood cell and platelet antigen genotyping are now available. Genotyping is a useful adjunct to traditional serology and can help resolve complex serologic problems. Although red blood cell and platelet phenotypes can be inferred from genotype, knowledge of the molecular basis is essential for accurate assignment. Genotyping of blood donors is an effective method of identifying antigen-negative and/or particularly rare donors. Cell-free DNA analysis provides a promising noninvasive method of assessing fetal genotypes of blood group alloantigens.

Pancreatic neoplasms, including ductal adenocarcinoma, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and pancreatoblastoma, are associated with different genetic abnormalities. Hepatic adenomas with beta-catenin exon 3 mutation are associated with a high risk of malignancy. Hepatic adenoma with arginosuccinate synthetase 1 expression or sonic hedgehog mutations are associated with a risk of bleeding. Hepatocellular carcinoma and choangiocarcinoma display heterogeneity at both morphologic and molecular levels Cholangiocellular carcinoma is most commonly associated with IDH 1/2 mutations.

The most significant contribution of molecular subtyping of breast carcinomas has been the identification of estrogen-positive and estrogen-negative tumor subtypes. Knowledge of genetic alterations in these tumors will help clinicians identify novel therapeutic targets. Understanding the progression pathways involved in the transition of in situ carcinoma to invasive carcinoma might lead to efficient risk stratification in these patients. The Cancer Genome Analysis Network has collected genomic and epigenomic data to provide comprehensive information regarding carcinogenesis and pathway interactions. Such information improves understanding of the disease process and also provides more accurate information toward identifying targetable mutations for treatment.

The unprecedented expansion of molecular pathology continues to affect and influence the clinical laboratory. Technological advances in high-throughput automation, cost containment, and refined methodology have improved the understanding of pathobiology through application of molecular pathology to multiple disease spaces. Incorporation of this field to emerging omics platforms, pharmacovigilance and biomarker discovery, and accessibility by lay consumers demonstrates the widespread reach of molecular pathology in the clinical marketplace. Pathologists should remain the stewards of this powerful and adaptable technology to provide guidance and appropriate laboratory application toward effective patient monitoring with respect to disease diagnosis and management.

MicroRNAs (miRNAs) are poised to provide diagnostic, prognostic, and therapeutic targets for several diseases including malignancies for precision medicine applications. The miRNAs have immense potential in the clinical arena because they can be detected in the blood, serum, tissues (fresh and formalin-fixed paraffin-embedded), and fine-needle aspirate specimens. The most attractive feature of miRNA-based therapy is that a single miRNA could be useful for targeting multiple genes that are deregulated in cancers, which can be further investigated through systems biology and network analysis that may provide cancer-specific personalized therapy.

Molecular biological techniques have evolved expeditiously and in turn have been applied to the detection of infectious disease. Maturation of these technologies and their coupling with related technological advancement in fluorescence, electronics, digitization, nanodynamics, and sensors among others have afforded clinical medicine additional tools toward expedient identification of infectious organisms at concentrations and sensitivities previously unattainable. These advancements have been adapted in select settings toward addressing clinical demands for more timely and effective patient management.

Ovarian carcinoma continues to be a concern for woman and maintains significant morbidity and mortality. Emerging molecular markers are providing additional opportunities for effective diagnosis and prognosis of disease. An integrated clinicopathologic and molecular classification of gynecologic malignancies has the potential to refine the clinical risk prediction of patients with cancer and to provide more tailored treatment recommendations.

The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis. Mismatch repair-deficient tumors have higher rates of programmed death-ligand 1 expression. Cell-free DNA analysis in fluids are proving beneficial for diagnosis and prognosis in these disease states towards effective patient management.

Molecular pathology techniques continue to evolve. Although polymerase chain reaction (PCR) remains the cornerstone methodology for nucleic acid amplification, improvements in nucleic acid detection methodologies (i.e. PCR) have increased the detection sensitivity by using fluorescent and bead based array technologies. Single base pair lesions can be detected via sequencing and related techniques to discern point mutations in disease pathogenesis. Novel technologies, such as high- resolution melting analysis, provide fast high throughput post PCR analysis of genetic mutations or variance in nucleic acid sequences. These and other technologies such as hybrid capture, fluorohore and chemiluminescence detections assays allow for rapid diagnosis and prognosis for expeditious and personalized patient management.

Esophageal cancer (EC) is rapidly increasing in incidence in the United States. Genetic changes associated with the development of EC involve the p16, p53, and APC genes. Human epidermal growth factor 2 (HER-2) overexpression is seen in gastroesophageal junction carcinoma and a subset gastric carcinoma (GC). Interestingly, up to 50% cases of GC are related to Helicobacter pylori infection and up to 16% are related to EBV infection. Microsatellite instability is observed in up to 39% of GC and cell free nucleic acid analysis provides additional opportunities for diagnosis and prognosis of disease.

In the last decade, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has seen enormous growth in routine toxicology laboratories. LC-MS/MS offers significant advantages over other traditional testing, such as immunoassay and gas chromatography-mass spectrometry methodologies. Major strengths of LC-MS/MS include improvement in specificity, flexibility, and sample throughput when compared with other technologies. Here, the basic principles of LC-MS/MS technology are reviewed, followed by advantages and disadvantages of this technology compared with other traditional techniques. In addition, toxicology applications of LC-MS/MS for simultaneous detection of large panels of analytes are presented.

This article presents an overview of forensic toxicology. The authors describe the three components that make up forensic toxicology: workplace drug testing, postmortem toxicology, and human performance toxicology. Also discussed are the specimens that are tested, the methods used, and how the results are interpreted in this particular discipline.

Although both the prevalence of asthma and the prescription drug use, notably the opiate analgesic class, epidemics are increasing, there is a complex interplay between both disorders, with both protective and exacerbating factors involved in the effect of opiates on asthma pathogenesis and clinical severity. This review examines the airway effects, both immunologic and neurologic, of opiates, which may interact and result in protection or exacerbation of asthma.

In this review, the authors address the general principles of prescribing psychiatric medications and discuss how the clinical laboratory can be used to guide prescribing practices. Treatment considerations in different settings and for different medications are discussed. Because the clinical laboratory is advancing in its technology, so should the clinician's knowledge of how to use the clinical laboratory. The authors propose recommendations and a simple algorithm for how to use medication levels in blood and other fluids to guide care in medications without well-defined therapeutic windows.

Toxicology testing in addiction medicine varies across the spectrum, yet remains a powerful tool in monitoring addictive patients. There are many reference laboratories offering toxicology testing, and physicians should have some understanding of laboratory, methodology, testing portfolio, and customer support structure to aid them in selecting the best toxicology laboratory for their patients. Consultation with a clinical pathologist/toxicologist in conjunction with the consideration of monitoring large numbers of illicit and psychoactive drugs in the addictive patient may provide important clinical information for their treatment.

About 75% of patients present to the emergency department with a complaint of pain. There are multiple prescribed and over-the-counter medications that are available for the treatment of pain. Acetaminophen, opioids, and aspirin are commonly used agents that are available as single agents or in combination with other medications. However, all of these agents are susceptible to toxic overdose, which requires prompt recognition through clinical and laboratory assessment modalities and initiation of therapy to reduce the risk of morbidity and mortality.

Pain management is an evolving discipline. New formulations mature with promises of improved pain control, better dosing, and fewer side effects. These agents also have an equal risk for abuse. Street chemists are adept at manipulating drugs to more potent versions and creating new compositions of matter. The clinical assessment of the patient is paramount to developing an index of suspicion of overdose, toxicity, or illicit drug use; the clinical laboratory can be a resource to support investigations and guide therapy. The clinical toxicology laboratory needs to keep in step, adapting technology and methodology to facilitate detection of such substances.

Drug addiction as a result of improper use of prescribed and illicit use has been on the increase globally. The effects of such use have implications in the urologic disease space. To this end, Ketamine has been reported to affect urologic function, causing a number of voiding symptoms. It may also confound the differential diagnosis of urologic diseases, such as interstitial cystitis, among others.

Precision medicine applies primarily to pharmacokinetics in toxicology. Mastering hepatic metabolism through an understanding of the genetics behind Phase I, or oxidation/reduction and some Phase II, or conjugation, enhances the scientific and clinical application of common drug toxicology. This review includes basic hepatic metabolism, the common substrates, inducers and inhibitors of cytochrome P450 along with genetic variants behind the enzymes. Detailed metabolism of commonly measured opioids in clinical practice is provided. Finally, evidence based research and clinical correlations conclude that knowledge of inducers and inhibitors, in conjunction with genetic variations, are integral components for applied precision medicine in toxicology.

Concern for illicit and restricted drug use in otolaryngology is similar to other surgical specialties with a few notable exceptions. Many illicit drugs are consumed transnasally. Repeated nasal exposure to stimulants or narcotics can cause local tissue destruction that can present as chronic rhinosinusitis or nasoseptal perforation. Further, the Food and Drug Administration has taken a stance against codeine for pediatric patients undergoing adenotonsillectomy. They have identified an increased risk of death postoperatively with these medications. Because codeine has been the most commonly prescribed narcotic, this has shifted the standard practice.

Interferences relating to laboratory toxicology testing refer to results which differ from their true value and are often encountered in the setting of a drug screen compared with confirmatory testing. Such interferences fall into two general categories; those that cause false positive results (when a drug screen is positive but confirmatory testing is negative) and those that cause false negative results (when a drug screen is negative when in reality the sample donor has ingested the tested substance). Such interferences can result from differences in laboratory testing methodology, reagent and analyte cross reactivity, limits of analyte detection, instrument resolution, reporting cutoff, sample processing, tissue type and sample adulteration among others. Awareness of the possible causes of such interferences are integral to proper laboratory result interpretation and patient management.

Scurvy is a nutritional disorder resulting from vitamin C deficiency. Although rare in developing countries, scurvy continues to develop in settings of limited dietary intake such as post-gastrointestinal surgery and restrictive dietary habits. The disease primarily affects the skin and soft tissue. As the state of deficiency persists, hematological and immunological sequelae may develop. The classic signs of scurvy are not always present and can be altered by the presence of other comorbidities. In this article, we present a challenging case of scurvy in an older male from an urban tertiary healthcare setting. We review the atypical and uncommon clinical and pathological findings of scurvy including those seen in the skin, blood, and bone marrow. We also review contemporary research findings that provide a better understanding of the pathogenicity and clinical manifestations of vitamin C deficiency.

Background Martial arts intervention in disease has been mostly limited to adult inflammatory, musculoskeletal, or motor diseases, where a mechanical intervention effects positive change. However, the application and benefit to pain management in childhood malignancy are not well described. Here, we assess the effects of defined martial arts intervention in children with cancer with respect to their pain perception and management. Methods Sixty-four children with childhood malignancies were enrolled in a martial arts program, which encompassed both meditation and movement modalities. Pain scores (0–10) were recorded pre- and post- 1-hour session intervention. Pain scores were crossed by total visits and tabulated by whether participant pain reduced at least 1 unit, stayed the same, or increased in intensity immediately after (post) participation session. Differences in pain scores were further compared by age and sex. Results Prepain and postpain scale data were measured for 64 participants, 43 males (67.2%) and 21 females (32.8%), ranging from 3 years to 19 years. Preintervention and postintervention data were obtained for 223 individual session visits. Mean number of patient participation visits was 1.8±1.6 (range one to nine visits). Of 116 individual measured sessions where the participants began with a pain score of at least 1, pain intensity reduced ≥1 unit in 85.3% (99/116) of visits, remained the same in 7.8% (9/116), and increased in 6.9% (8/116). For the majority (96.3%; 77/80) of sessions, participants began with a prepain intensity score of at least 5–10 with reduction in pain intensity following the session. The overall mean pain score presession visit was reduced bŷ40% (pre: 5.95±2.64 and post: 3.03±2.45 [95% CI: 2.34–3.50]; P≤0.001). Median pain intensity scores had greater reductions with increased age of participants (3–6 years [–1], 7–10 years [–2], 11–14 years [–3], and 15–19 years [–4]). Conclusion Martial arts intervention can provide a useful modality to decrease pain in childhood cancer, with greater effect achieved with higher baseline pain scores and patient age. Martial arts intervention may improve patient compliance with respect to medical and surgical management, thus reducing disease morbidity and health care costs., Video abstract

Virtually all the red blood cell and platelet antigen systems have been characterized at the molecular level. Highly reliable methods for red blood cell and platelet antigen genotyping are now available. Genotyping is a useful adjunct to traditional serology and can help resolve complex serologic problems. Although red blood cell and platelet phenotypes can be inferred from genotype, knowledge of the molecular basis is essential for accurate assignment. Genotyping of blood donors is an effective method of identifying antigen-negative and/or particularly rare donors. Cell-free DNA analysis provides a promising noninvasive method of assessing fetal genotypes of blood group alloantigens.

MicroRNAs (miRNAs) are poised to provide diagnostic, prognostic, and therapeutic targets for several diseases including malignancies for precision medicine applications. The miRNAs have immense potential in the clinical arena because they can be detected in the blood, serum, tissues (fresh and formalin-fixed paraffin-embedded), and fine-needle aspirate specimens. The most attractive feature of miRNA-based therapy is that a single miRNA could be useful for targeting multiple genes that are deregulated in cancers, which can be further investigated through systems biology and network analysis that may provide cancer-specific personalized therapy.

Neoplasms of the small intestine are rare in comparison with colorectal tumors. The most common tumor types arising in the small intestine are adenocarcinomas, well-differentiated neuroendocrine tumors, gastrointestinal stromal tumors, and lymphoma. Primary appendiceal neoplasms are rare and found in less than 2% of appendectomy specimens with an incidence of approximately 1.2 cases per 100,000 people per year in the United States. This article explores molecular diagnostics in the neoplasms of small intestine and appendix.

Esophageal cancer (EC) is rapidly increasing in incidence in the United States. Genetic changes associated with the development of EC involve the p16, p53, and APC genes. Human epidermal growth factor 2 (HER-2) overexpression is seen in gastroesophageal junction carcinoma and a subset gastric carcinoma (GC). Interestingly, up to 50% cases of GC are related to Helicobacter pylori infection and up to 16% are related to EBV infection. Microsatellite instability is observed in up to 39% of GC and cell free nucleic acid analysis provides additional opportunities for diagnosis and prognosis of disease.

Molecular genetic technologies are used to aid in diagnosis and treatment of borderline melanocytic tumors as an adjuvant to the gold standard histopathologic evaluation. A specific set of fluorescence in situ hybridization probes is widely used to aid in diagnosing challenging melanocytic lesions. New melanoma probe cocktails have revealed increased sensitivity and specificity in ambiguous melanocytic cases. Array comparative genomic hybridization is a more complex technology used for the work-up of diagnostically problematic Spitzoid melanocytic proliferations. Cutting-edge technologies, including next-generation sequencing and cell-free nucleic acid analysis, are promising biomarker applications for mutation detection towards personalized patient management.

The most significant contribution of molecular subtyping of breast carcinomas has been the identification of estrogen-positive and estrogen-negative tumor subtypes. Knowledge of genetic alterations in these tumors will help clinicians identify novel therapeutic targets. Understanding the progression pathways involved in the transition of in situ carcinoma to invasive carcinoma might lead to efficient risk stratification in these patients. The Cancer Genome Analysis Network has collected genomic and epigenomic data to provide comprehensive information regarding carcinogenesis and pathway interactions. Such information improves understanding of the disease process and also provides more accurate information toward identifying targetable mutations for treatment.

Ovarian carcinoma continues to be a concern for woman and maintains significant morbidity and mortality. Emerging molecular markers are providing additional opportunities for effective diagnosis and prognosis of disease. An integrated clinicopathologic and molecular classification of gynecologic malignancies has the potential to refine the clinical risk prediction of patients with cancer and to provide more tailored treatment recommendations.

Molecular pathology techniques continue to evolve. Although polymerase chain reaction (PCR) remains the cornerstone methodology for nucleic acid amplification, improvements in nucleic acid detection methodologies (i.e. PCR) have increased the detection sensitivity by using fluorescent and bead based array technologies. Single base pair lesions can be detected via sequencing and related techniques to discern point mutations in disease pathogenesis. Novel technologies, such as high- resolution melting analysis, provide fast high throughput post PCR analysis of genetic mutations or variance in nucleic acid sequences. These and other technologies such as hybrid capture, fluorohore and chemiluminescence detections assays allow for rapid diagnosis and prognosis for expeditious and personalized patient management.

The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis. Mismatch repair-deficient tumors have higher rates of programmed death-ligand 1 expression. Cell-free DNA analysis in fluids are proving beneficial for diagnosis and prognosis in these disease states towards effective patient management.