The effectiveness of early interventions for post-stroke spasticity: a systematic review.

PURPOSE: To synthesize evidence on the effect of early post-stroke spasticity interventions. METHODS: Systematic literature search (PubMed, Embase, and Web of Science) encompassing studies on spasticity reducing interventions within 3 months post stroke on outcome defined within the International Classification of Functioning (ICF). RESULTS: In total, 27 studies were identified with n = 1.658 cases. Botulinum toxin (2-12 weeks; 10 studies, n = 794) showed consistent and significant reduced spasticity by Modified Ashworth Scale (MAS) or electromyography (EMG). Electrical muscle stimulation (1-8 weeks; 6 studies, n = 335) showed lower MAS/Composite Spasticity Scale scores in 4 studies. Transcranial stimulation (3 studies; n = 131), oral spasmolytics (1 study; n = 38), shockwave (1 study; n = 40), orthotics (3 studies; n = 197 and robot-assisted therapy (3 studies; n = 123) showed inconclusive results. Effects on ICF activity domain could not be established due to limited data and large outcome measures heterogeneity. One out of two studies showed significant benefit for early compared to late BoNT intervention (< 90 vs> 90 days). CONCLUSION: This study provides evidence for early applied (<3 months) BoNT to effectively reduce spasticity and probable effectiveness of electrical stimulation. Establishing effects of interventions in the acute/hospitalization phase (<7 days) needs further work, specifically on the ICF activity domain. Standardization of outcome measures is required.

Spasticity, which may develop in the first weeks after stroke, is now mostly treated in the chronic phase.This study shows that early applied Botulinum Toxin (within three months after stroke) effectively reduces spasticity and suggests that electrical stimulation may reduce spasticity.Early application of treatment with Botulinum Toxin should be considered when spasticity occurs within three months post-stroke.

Tumor glómico causante de dolor de dedo crónico: la prueba de detección de isquemia es un signo clínico fiable para su diagnóstico. Informe de un caso y revisión de la literatura / Glomus tumor causing chronic finger pain: Ischemia test is a reliable clinical sign for the diagnosis. Case report and review of literature

Los tumores glómicos (TG) son neoplasias benignas raras, que se derivan de la estructura neuroarterial denominada cuerpo glómico, un shunt arteriovenoso especializado implicado en la regulación de la temperatura. Representan menos de 2% de los tumores del tejido blando, y entre 1 y 4,5% de los tumores de la mano. Aun cuando sus primeras descripciones aparecieron hace casi 100 años, son comunes la demora y la ausencia diagnósticas, las cuales originan un sufrimiento terrible. La tríada diagnóstica clásica consiste en dolor espontáneo, sensación de presión y sensibilidad, e hipersensibilidad al frío. La imagen de resonancia magnética (IRM) sigue siendo la modalidad de imagen más útil. La supresión del dolor tras inflar un esfigmomanómetro por encima de los niveles de la presión arterial sistólica (prueba de detección de isquemia) es altamente diagnóstica, por lo que sugerimos el uso rutinario de esta prueba simple en los casos de dolor en la extremidad superior de etiología desconocida. La resección quirúrgica es el tratamiento de elección, y es curativa. (AU)

Glomus tumors are a rare benign neoplasm arising from the neuroarterial structure called the glomus body, a specialized arteriovenous shunt involved in temperature regulation. They represent less than 2% of soft tissue tumors and between 1 and 4.5% of hand's tumors. Even though its first descriptions appeared almost 100 years ago, late and missed diagnoses are common, which leads to terrible suffering. The classic diagnostic triad consists of spontaneous pain, pressure sensation and tenderness, and cold hypersensitivity. Magnetic resonance imaging stills the most useful imaging modality. Abolition of pain after inflating a blood pressure cuff above systolic blood pressure levels (ischemia test) is highly diagnostic, so we suggest the routine use of this simple test in cases of upper limb pain of unknown etiology clear. Surgical excision is the treatment of choice and is curative. (AU)

Outcomes of Thumb Metacarpophalangeal Joint Arthrodesis Using the XMCP Intramedullary Interlocking Device.

Purpose: The intramedullary interlocking device for metacarpophalangeal (MCP) joint arthrodesis (XMCP, Extremity Medical, Parsippany, NJ) has been shown to promote union at a precise angle, provide strong fixation without the need for prolonged immobilization, and lower the incidence of hardware irritation and revision surgery. In this study, we evaluated the clinical outcomes of patients undergoing MCP joint arthrodesis with the XMCP system using a retrospective chart review, patient reported outcomes, and radiographic analysis. Methods: A retrospective chart review and phone survey was conducted on 57 patients (58 cases) from a single institution between 2017 and 2022. The primary outcome was patient satisfaction, including pre- and postoperative Numeric Rating Scale (NRS) pain scores, Disabilities of Arm Shoulder and Hand (QuickDASH) outcomes, perceived grip strength, and willingness to undergo the procedure again. Secondary outcomes included the need for revision procedures, successful fusion of arthrodesis, and postoperative complications. Results: Of the 57 patients who underwent MCP joint arthrodesis of the thumb using the XMCP fusion device, a total of 43 (75%) completed the phone survey. The average age of patients was 67 years with an average clinical follow-up of 9 months (range 1-65 months). Patients who participated in the phone survey questionnaire had an average QuickDASH score of 24.7 ± 20.5. Average perceived NRS scores were 6.2 ± 3.5 and 1.2 ± 2.1 before and after surgery, respectively. Average perceived grip strength of patients was 3 ± 1.3 out of 5. When evaluating for concurrent procedures, there was no statistically significant difference in pre- or postoperative NRS scores. In total, 38 (88%) patients were satisfied with the procedure, and 39 (91%) patients would undergo the procedure again. Conclusion: Metacarpophalangeal joint arthrodesis of the thumb with the intramedullary fusion device is reproducible, allows for immediate use without immobilization, has a low number of complications, and provides improved function and pain relief. Level of Evidence: Therapeutic III.

Glomus tumor causing chronic finger pain: ischemia test is a reliable clinical sign for the diagnosis. Case report and review of literature.

Glomus tumors are a rare, benign neoplasm arising from the neuroarterial structure known as the glomus body, which is a specialized arteriovenous shunt involved in temperature regulation. They account for less than 2% of soft tissue tumors and between 1% and 4.5% of tumors in the hand.. Despite their first descriptions appearing almost 100 years ago, late and missed diagnoses are common, leading to significant suffering. The classic diagnostic triad includes spontaneous pain, a sensation of pressure and tenderness, and cold hypersensitivity. Magnetic resonance imaging remains the most useful imaging modality. The abolition of pain after inflating a blood pressure cuff above the systolic blood pressure level (ischemia test) is highly diagnostic.Therefore, we suggest the routine use of this simple test in cases of upper limb pain of unclear etiology . Surgical excision is the treatment of choice and is curative.

Epidemiology of and Risk Factors for Table Saw Injuries of the Hands and Fingers.

Purpose: The purpose of this study was to evaluate circumstances surrounding power saw injuries. We hypothesized that power saw injuries are caused by either inexperienced or inappropriate usage of saws. Methods: A retrospective review of patients at our level 1 trauma center from January 2011 to April 2022 was conducted. Patients were screened using surgical billing records based on Current Procedural Terminology codes. Codes associated with revascularization; amputation of digits; and repair of tendon, nerve, and open metacarpal and phalanx fractures were queried. Patients who sustained power saw injuries were identified. They were then contacted by phone, and a standardized questionnaire was administered. Verbal consent was included in the standardized script, which was approved by the institutional review board. Results: One hundred eleven patients were identified who underwent surgical treatment for power saw injuries of the hands. Of them, we were able to contact 44 patients, who consented to and completed the questionnaire. Of all of the contacted patients, 40 (91%) were men, with an average age of 55 years (range, 27-80 years). No patients were intoxicated when the injury occurred. Thirty-two (73%) patients had used the same saw for more than 25 times. Sixteen (36%) patients had not received formal training regarding safe use of their saw, and 7 (16%) had removed a safety mechanism prior to the injury. Thirteen (30%) patients had used the saw on an unstable surface, and 17 (39%) reported not having changed the saw blade regularly. Conclusions: Power saw injuries occur for a multitude of reasons. Contrary to our hypothesis, more experience with the use of saws does not necessarily protect one from saw injuries. These findings highlight the need for formal training among new saw users and continuing education for the more experienced to help reduce the incidence of saw injuries that require surgical intervention. Type of study/level of evidence: Prognostic IV.

Outcomes Following Repeat Collagenase Treatment of Dupuytren Contracture.

PURPOSE: Injectable collagenase Clostridium histolyticum has been an effective and well-tolerated nonsurgical treatment option for the management of Dupuytren contracture of the hand. The purpose of this study was to determine the efficacy of collagenase injection and adverse event rate in patients who had undergone previous collagenase treatment. METHODS: A retrospective chart review was performed on 332 patients treated with collagenase injection for Dupuytren contracture by three fellowship-trained hand surgeons at a single institution from 2009 to 2019. Fifty-nine joints in 45 patients underwent repeat collagenase therapy for recurrent contracture in the same digit. Pretreatment and posttreatment total metacarpophalangeal and proximal interphalangeal joint flexion contractures were recorded, with complete correction defined as <5° residual digital flexion contracture. Postmanipulation skin tears and adverse events were recorded. A comparison was made between average contracture improvement after initial collagenase injection and that after repeat injection. RESULTS: Forty-five patients with an average duration of 30 months (range, 6-73 months) between initial and repeat collagenase therapies were identified. The mean improvement after first collagenase injection was 45° ± 24° (39° for metacarpophalangeal joint and 50° for proximal interphalangeal joint) compared with a mean improvement of 43° ± 23° (41° for metacarpophalangeal joint and 44° for proximal interphalangeal joint) after second injection. Although similar complete correction rates and skin tear rates (32.2 % for initial and 30.5% for repeat) were observed between initial (80%) and repeat injections (73%), the occurrence of adverse events was 3 times higher (3.4% for initial and 10.2% for repeat) in the latter group. CONCLUSIONS: Collagenase treatment of Dupuytren contracture yields effective total flexion contracture correction. Repeat collagenase treatment of previously treated digits yields similar deformity correction and complete correction rates but a higher incidence of adverse events. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Race/ethnicity and advanced stage of renal cell carcinoma in adults: results from surveillance, epidemiology, and end results program 2007-2015.

Non-Hispanic Blacks were shown to have an earlier stage of renal cell carcinoma (RCC) at diagnosis compared to non-Hispanic Whites. It is less clear whether disparities in RCC staging occurs for other minority races/ethnicities. We aimed to assess the association between racial/ethnic minorities and stage at diagnosis of RCC, and test for potential effect modification by histological subtype. Sourced from the Surveillance, Epidemiology and End Results (SEER) database, patients ≥20 years diagnosed with RCC from 2007 to 2015 were included (n = 37 493). Logistic regression analyses were performed to assess the independent association between race/ethnicity [non-Hispanic White, non-Hispanic Black, non-Hispanic Asian Pacific Islander, non-Hispanic American Indian/Alaskan Native (AI/AN) and Hispanic] and advanced RCC stage at diagnosis (i.e. regional spread or distant metastasis). Interaction terms were tested and stratified regression was performed accordingly. Twenty-eight percent of patients had advanced RCC stage at diagnosis. After adjusting for age, gender, year of diagnosis, histological subtype and insurance status, compared to non-Hispanic Whites, non-Hispanic Blacks had lower odds of advanced stage at diagnosis [odds ratio (OR) = 0.79; 95% confidence interval (CI) = 0.72-0.87 for clear cell; OR = 0.48; CI = 0.30-0.78 for chromophobe and OR = 0.26; CI = 0.10-0.35 for other subtypes]. Higher odds of advanced stage at diagnosis were found for non-Hispanic AI/AN in clear cell (OR = 1.27; CI = 1.04-1.55) and for Hispanics in papillary subtypes (OR = 1.58; CI = 1.07-2.33). Racial disparities in the RCC stage at diagnosis varied according to histological subtype. Further investigation on the racial disparities reported is warranted to optimize detection and ultimately improve the prognosis of patients with RCC.

A Comparative Analysis on the Career Perceptions of Tourism Management Students Before and During the COVID-19 Pandemic.

The serious impact of the COVID-19 pandemic also affected educational institutions offering tourism programs and students' perceptions of their future career in the industry. The study determined and compared the career perceptions of Tourism Management students in Far Eastern University Manila, Philippines before and during the COVID-19 pandemic with the end view of providing significant inputs to the development of programs for the tourism students in relation to their career opportunities. Using the mixed methods approach and the simple random and purposive sampling techniques, 196 third year tourism management students enrolled in AY 2020-2021 in a private Institution in Manila, Philippines completed the researcher-made survey questionnaire to gather quantitative data. On the other hand, focus group discussion (FGD) was conducted on six pre-selected student-participants to collect qualitative data. The use of a paired sample T-Test proved that there is a significant difference in the student career perception before and during the pandemic. The qualitative findings revealed that: 1) the Tourism Industry as a major business sector was severely affected by the COVID-19 pandemic; 2) the students perceive their career opportunities in the Tourism Industry during this pandemic as full of uncertainties; 3) implementing a relevant and timely program that will address the students' wants and needs must be put into action to help the students adapt to the current situation. Accordingly, Higher Educational Institutions (HEIs) are encouraged to provide the students a more comprehensive student career opportunity program that will address the changes in student career perceptions and uncertainties on their future career opportunities in the Tourism Industry.

Low sustainability of weight loss among patients with non-alcoholic fatty liver disease

Background@#Weight loss, though difficult to attain and sustain over time, remains the cornerstone of non-alcoholic fatty liver disease (NAFLD) treatment. We aimed to describe weight changes among NAFLD patients. @*Methods@#This was a retrospective, cohort study of consecutively-identified NAFLD patients with >2 clinic visits from March2007–April2018. Weight changes from baseline were categorized into weight gain, weight loss, and no change. Baseline liver and metabolic biochemistries and non-invasive liver fibrosis tests were correlated with the final weight changes. Succeeding weight changes after the initial follow-up visits were used to determine sustainability of weight loss. @*Results@#Of the 240 patients included, 123 (51.2%), 93 (38.8%), and 24 (10%) had weight gain, weight loss, and no change, respectively. Only 12.5% had >5% weight loss. Duration of follow-up was significantly longer for patients with weight loss (p<0.001). None of the baseline demographic and laboratory data were associated with weight loss. Patients with weight loss also did not have significant changes to their biochemistries and non-invasive liver fibrosis tests compared to patients with weight gain/no change. Compared to patients with weight gain after the initial follow-up, where only 11.8% were able to lose weight on the final visit, 73.1% of patients who lost weight after the initial follow-up were able to sustain their weight loss on the final visit. @*Conclusions@#Weight loss is achieved in only a third of NAFLD patients. Although 73% of patients who lost weight initially were able to sustain it, patients who gained weight after the 1st follow-up were unlikely to lose weight on further follow-up.

Transcriptional regulation of genes bearing intronic heterochromatin in the rice genome.

Intronic regions of eukaryotic genomes accumulate many Transposable Elements (TEs). Intronic TEs often trigger the formation of transcriptionally repressive heterochromatin, even within transcription-permissive chromatin environments. Although TE-bearing introns are widely observed in eukaryotic genomes, their epigenetic states, impacts on gene regulation and function, and their contributions to genetic diversity and evolution, remain poorly understood. In this study, we investigated the genome-wide distribution of intronic TEs and their epigenetic states in the Oryza sativa genome, where TEs comprise 35% of the genome. We found that over 10% of rice genes contain intronic heterochromatin, most of which are associated with TEs and repetitive sequences. These heterochromatic introns are longer and highly enriched in promoter-proximal positions. On the other hand, introns also accumulate hypomethylated short TEs. Genes with heterochromatic introns are implicated in various biological functions. Transcription of genes bearing intronic heterochromatin is regulated by an epigenetic mechanism involving the conserved factor OsIBM2, mutation of which results in severe developmental and reproductive defects. Furthermore, we found that heterochromatic introns evolve rapidly compared to non-heterochromatic introns. Our study demonstrates that heterochromatin is a common epigenetic feature associated with actively transcribed genes in the rice genome.

Rice Histone Propionylation and Generation of Chemically Derivatized Synthetic H3 and H4 Peptides for Identification of Acetylation Sites and Quantification.

Histone proteins are crucial in the study of chromatin dynamics owing to their wide-ranging implications in the regulation of gene expression. Modifications of histones are integral to these regulatory processes in concert with associated proteins, such as transcription factors and coactivators. One of the biochemical techniques available to enhance analysis of histone proteins is chemical derivatization using propionic anhydride. In this protocol, we describe the use of propionylation to efficiently derivatize acid-extracted histones from rice. We also synthesize H3 and H4 tryptic peptides, thus mimicking the nature of derivatized extracted peptides to aid in identification and quantification using targeted-mass spectrometry. Here we make available the masses of the precursor ions and the retention times (RT) of each synthesized peptide. These provide useful information to facilitate histone data analysis. Lastly, we note that we will distribute these synthetic peptides in nanomolar (nM) concentrations to those who wish to utilize them for assays and further experimental studies.

Pulmonary function and respiratory health after successful treatment of drug-resistant tuberculosis.

BACKGROUND: Post-treatment morbidity among subjects with drug-resistant tuberculosis (DR-TB) is unclear. METHODS: This was a cross-sectional study of patients from Tbilisi, Georgia with cavitary DR-TB and an outcome of cure. Participants had a chest X-ray (CXR), St. George Respiratory Quality (SGRQ) survey, and pulmonary function tests (PFTs) performed. Correlations between SGRQ and PFT results and factors associated with pulmonary impairment were examined. RESULTS: Among 58 subjects (median age 31 years), 40% used tobacco, 59% had prior TB, and 47% underwent adjunctive surgical resection. The median follow-up time was 41 months. Follow-up CXR revealed fibrosis in 30 subjects (52%) and bronchiectasis in seven (12%). The median forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio was 0.72, with 24 subjects (41%) having a ratio of ≤0.70. Significant correlations existed between PFT measures and overall and component SGRQ scores. In linear regression, age, prior TB, and CXR fibrosis or bronchiectasis were significantly associated with decreased pulmonary function. Adjunctive surgery was significantly associated with a higher percent predicted FEV1 and FVC. CONCLUSIONS: A high proportion of DR-TB subjects had residual pulmonary impairment, particularly with recurrent TB and severe radiological disease. The association of surgical resection with improved lung function deserves further study. PFTs and SGRQ may both be useful to evaluate lung health.

Proteolytic System of Streptococcus thermophilus.

The growth of lactic acid bacteria (LAB) generates a high number of metabolites related to aromas and flavors in fermented dairy foods. These microbial proteases are involved in protein hydrolysis that produces necessary peptides for their growth and releases different molecules of interest, like bioactive peptides, during their activity. Each genus in particular has its own proteolytic system to hydrolyze the necessary proteins to meet its requirements. This review aims to highlight the differences between the proteolytic systems of Streptococcus thermophilus and other lactic acid bacteria (Lactococcus and Lactobacillus) since they are microorganisms that are frequently used in combination with other LAB in the elaboration of fermented dairy products. Based on genetic studies and in vitro and in vivo tests, the proteolytic system of Streptococcus thermophilus has been divided into three parts: 1) a serine proteinase linked to the cellular wall that is activated in the absence of glutamine and methionine; 2) the transport of peptides and oligopeptides, which are integrated in both the Dpp system and the Ami system, respectively; according to this, it is worth mentioning that the Ami system is able to transport peptides with up to 23 amino acids while the Opp system of Lactococcus or Lactobacillus transports chains with less than 13 amino acids; and finally, 3) peptide hydrolysis by intracellular peptidases, including a group of three exclusive of S. thermophilus capable of releasing either aromatic amino acids or peptides with aromatic amino acids.

Allocation of Heme Is Differentially Regulated by Ferrochelatase Isoforms in Arabidopsis Cells.

Heme is involved in various biological processes as a cofactor of hemoproteins located in various organelles. In plant cells, heme is synthesized by two isoforms of plastid-localized ferrochelatase, FC1 and FC2. In this study, by characterizing Arabidopsis T-DNA insertional mutants, we showed that the allocation of heme is differentially regulated by ferrochelatase isoforms in plant cells. Analyses of weak (fc1-1) and null (fc1-2) mutants suggest that FC1-producing heme is required for initial growth of seedling development. In contrast, weak (fc2-1) and null (fc2-2) mutants of FC2 showed pale green leaves and retarded growth, indicating that FC2-producing heme is necessary for chloroplast development. During the initial growth stage, FC2 deficiency caused reduction of plastid cytochromes. In addition, although FC2 deficiency marginally affected the assembly of photosynthetic reaction center complexes, it caused relatively larger but insufficient light-harvesting antenna to reaction centers, resulting in lower efficiency of photosynthesis. In the later vegetative growth, however, fc2-2 recovered photosynthetic growth, showing that FC1-producing heme may complement the FC2 deficiency. On the other hand, reduced level of cytochromes in microsomal fraction was discovered in fc1-1, suggesting that FC1-producing heme is mainly allocated to extraplastidic organelles. Furthermore, the expression of FC1 is induced by the treatment of an elicitor flg22 while that of FC2 was reduced, and fc1-1 abolished the flg22-dependent induction of FC1 expression and peroxidase activity. Consequently, our results clarified that FC2 produces heme for the photosynthetic machinery in the chloroplast, while FC1 is the housekeeping enzyme providing heme cofactor to the entire cell. In addition, FC1 can partly complement FC2 deficiency and is also involved in defense against stressful conditions.

Epigenetic Control of Defense Signaling and Priming in Plants.

Immune recognition of pathogen-associated molecular patterns or effectors leads to defense activation at the pathogen challenged sites. This is followed by systemic defense activation at distant non-challenged sites, termed systemic acquired resistance (SAR). These inducible defenses are accompanied by extensive transcriptional reprogramming of defense-related genes. SAR is associated with priming, in which a subset of these genes is kept at a poised state to facilitate subsequent transcriptional regulation. Transgenerational inheritance of defense-related priming in plants indicates the stability of such primed states. Recent studies have revealed the importance and dynamic engagement of epigenetic mechanisms, such as DNA methylation and histone modifications that are closely linked to chromatin reconfiguration, in plant adaptation to different biotic stresses. Herein we review current knowledge regarding the biological significance and underlying mechanisms of epigenetic control for immune responses in plants. We also argue for the importance of host transposable elements as critical regulators of interactions in the evolutionary "arms race" between plants and pathogens.

Age protects from harmful effects produced by chronic intermittent hypoxia.

Obstructive sleep apnoea (OSA) affects an estimated 3­7% of the adult population, the frequency doubling at ages >60­65 years. As it evolves, OSA becomes frequently associated with cardiovascular, metabolic and neuropsychiatric pathologies defining OSA syndrome (OSAS). Exposing experimental animals to chronic intermittent hypoxia (CIH) can be used as a model of the recurrent hypoxic and O2 desaturation patterns observed in OSA patients. CIH is an important OSA event triggering associated pathologies; CIH induces carotid body (CB)-driven exaggerated sympathetic tone and overproduction of reactive oxygen species, related to the pathogenic mechanisms of associated pathologies observed in OSAS. Aiming to discover why OSAS is clinically less conspicuous in aged patients, the present study compares CIH effects in young (3­4 months) and aged (22­24 months) rats. To define potential distinctive patterns of these pathogenic mechanisms, mean arterial blood pressure as the final CIH outcome was measured. In young rats, CIH augmented CB sensory responses to hypoxia, decreased hypoxic ventilation and augmented sympathetic activity (plasma catecholamine levels and renal artery content and synthesis rate). An increased brainstem integration of CB sensory input as a trigger of sympathetic activity is suggested. CIH also caused an oxidative status decreasing aconitase/fumarase ratio and superoxide dismutase activity. In aged animals, CIH minimally affected CB responses, ventilation and sympathetic-related parameters leaving redox status unaltered. In young animals, CIH caused hypertension and in aged animals, whose baseline blood pressure was augmented, CIH did not augment it further. Plausible mechanisms of the differences and potential significance of these findings for the diagnosis and therapy of OSAS are discussed.

Experimental Observations on the Biological Significance of Hydrogen Sulfide in Carotid Body Chemoreception.

The cascade of transduction of hypoxia and hypercapnia, the natural stimuli to chemoreceptor cells, is incompletely understood. A particular gap in that knowledge is the role played by second messengers, or in a most ample term, of modulators. A recently described modulator of chemoreceptor cell responses is the gaseous transmitter hydrogen sulfide, which has been proposed as a specific activator of the hypoxic responses in the carotid body, both at the level of the chemoreceptor cell response or at the level of the global output of the organ. Since sulfide behaves in this regard as cAMP, we explored the possibility that sulfide effects were mediated by the more classical messenger. Data indicate that exogenous and endogenous sulfide inhibits adenyl cyclase finding additionally that inhibition of adenylyl cyclase does not modify chemoreceptor cell responses elicited by sulfide. We have also observed that transient receptor potential cation channels A1 (TRPA1) are not regulated by sulfide in chemoreceptor cells.

The influence of disease risk on the optimal time interval between screens for the early detection of cancer: a mathematical approach.

The intervals between screens for the early detection of diseases such as breast and colon cancer suggested by screening guidelines are typically based on the average population risk of disease. With the emergence of ever more biomarkers for cancer risk prediction and the development of personalized medicine, there is a need for risk-specific screening intervals. The interval between successive screens should be shorter with increasing cancer risk. A risk-dependent optimal interval is ideally derived from a cost-effectiveness analysis using a validated simulation model. However, this is time-consuming and costly. We propose a simplified mathematical approach for the exploratory analysis of the implications of risk level on optimal screening interval. We develop a mathematical model of the optimal screening interval for breast cancer screening. We verified the results by programming the simplified model in the MISCAN-Breast microsimulation model and comparing the results. We validated the results by comparing them with the results of a full, published MISCAN-Breast cost-effectiveness model for a number of different risk levels. The results of both the verification and validation were satisfactory. We conclude that the mathematical approach can indicate the impact of disease risk on the optimal screening interval.

Positive C4d in kidney transplantation biopsy: clinical impact.

BACKGROUND: Deposition of C4d in peritubular capillaries of renal graft is normally associated with the presence of antibody-mediated rejection. The clinical impact of its presence in patients with renal transplant in Colombia is uncertain, as well as the association in acute rejection and the response to the management and survival of the graft. The aim of this study was to determine the risk of having positive C4d in biopsies of patients with episodes of acute cellular rejection. METHODS: We retrospectively reviewed 226 biopsies of kidney transplantation, all of them with acute rejection and histopathological findings classified according to Banff criteria 2009 and performed between January 2005 and December 2012 for graft dysfunction. C4d staining was performed by immunohistochemistry. RESULTS: C4d staining was positive in 25 of 226 biopsies. Rejection time in patients with positive C4d was 15 months in average vs 8 months with negative C4d. CONCLUSIONS: With the use of a multivariate analysis, we found that the unique risk for C4d in our population was the positive panel reactive antibodies and elapsed time between transplant and the rejection (odds ratio: 2.12, P = .034) and that the other variables analyzed are not related to the expression of C4d.

Effects of rosiglitazone vs metformin on circulating osteoclast and osteogenic precursor cells in postmenopausal women with type 2 diabetes mellitus.

CONTEXT: Thiazolidinediones are associated with increased fractures in type 2 diabetes mellitus (T2D). One explanation is that activation of peroxisome proliferator-activated receptor-γ expression alters bone remodeling cells. OBJECTIVE: To investigate whether osteoclast and osteogenic precursor cells are altered by rosiglitazone (RSG) treatment in T2D as compared to metformin (MET) treatment. DESIGN: A randomized controlled trial of RSG or MET for 52 weeks, followed by 24 weeks of MET. SETTING: Data were generated at a tertiary care center. PATIENTS: Seventy-three T2D postmenopausal women participated. MAIN OUTCOME MEASURES: Peripheral blood mononuclear cells were isolated and cultured with receptor activator of nuclear factor κB ligand and stained for tartrate-resistant acid phosphatase to measure circulating osteoclast precursors. Peripheral blood mononuclear cells were also characterized for osteogenic, endothelial, and calcification markers by flow cytometry with the ligands osteocalcin (OCN), CD34, and CD 146. RESULTS: Tartrate-resistant acid phosphatase-positive cells increased between weeks 0 and 52 (RSG, 2.9 ± 2 to 14.0 ± 3 U/L, P = .001; MET, 3.3 ± 2 to 16.7 ± 2 U/L, P = .001), increasing further in the RSG group after changing to MET (to 26.5 ± 5 U/L, P = .05 vs wk 52). With RSG, OCN+ cells with CD34 but without CD146 fell from weeks 0 to 52 (20.1 ± 1% to 15.5 ± 2%; P = .03), remaining stable through week 76. The OCN+ cells lacking both CD34 and CD146 increased from weeks 0 to 52 (67.3 ± 2 to 74.4 ± 2%; P = .02), but returned to baseline after switching to MET. CONCLUSION: In postmenopausal women with T2D, circulating osteoclast precursor cells increase with both RSG and MET, and increase further when switching from RSG to MET. Subpopulations of cells that may be involved in the osteogenic lineage pathway are also altered with RSG. Further work is necessary to elucidate how these changes may relate to fracture risk.