Computational Hyperspectral Microflow Cytometry.

Miniaturized flow cytometry has significant potential for portable applications, such as cell-based diagnostics and the monitoring of therapeutic cell manufacturing, however, the performance of current techniques is often limited by the inability to resolve spectrally-overlapping fluorescence labels. Here, the study presents a computational hyperspectral microflow cytometer (CHC) that enables accurate discrimination of spectrally-overlapping fluorophores labeling single cells. CHC employs a dispersive optical element and an optimization algorithm to detect the full fluorescence emission spectrum from flowing cells, with a high spectral resolution of ≈3 nm in the range from 450 to 650 nm. CHC also includes a dedicated microfluidic device that ensures in-focus imaging through viscoelastic sheathless focusing, thereby enhancing the accuracy and reliability of microflow cytometry analysis. The potential of CHC for analyzing T lymphocyte subpopulations and monitoring changes in cell composition during T cell expansion is demonstrated. Overall, CHC represents a major breakthrough in microflow cytometry and can facilitate its use for immune cell monitoring.

Cytochrome c levels affect the TOR pathway to regulate growth and metabolism under energy-deficient conditions.

Mitochondrial function is essential for plant growth, but the mechanisms involved in adjusting growth and metabolism to changes in mitochondrial energy production are not fully understood. We studied plants with reduced expression of CYTC-1, one of two genes encoding the respiratory chain component cytochrome c (CYTc) in Arabidopsis, to understand how mitochondria communicate their status to coordinate metabolism and growth. Plants with CYTc deficiency show decreased mitochondrial membrane potential and lower ATP content, even when carbon sources are present. They also exhibit higher free amino acid content, induced autophagy, and increased resistance to nutritional stress caused by prolonged darkness, similar to plants with triggered starvation signals. CYTc deficiency affects target of rapamycin (TOR)-pathway activation, reducing S6 kinase (S6K) and RPS6A phosphorylation, as well as total S6K protein levels due to increased protein degradation via proteasome and autophagy. TOR overexpression restores growth and other parameters affected in cytc-1 mutants, even if mitochondrial membrane potential and ATP levels remain low. We propose that CYTc-deficient plants coordinate their metabolism and energy availability by reducing TOR-pathway activation as a preventive signal to adjust growth in anticipation of energy exhaustion, thus providing a mechanism by which changes in mitochondrial activity are transduced to the rest of the cell.

Single Nucleotide Polymorphisms Associated with Prostate Cancer Progression: A Systematic Review.

BACKGROUND: New biomarkers of progression in patients with prostate cancer (PCa) are needed to improve their classification and clinical management. This systematic review investigated the relationship between single nucleotide polymorphisms (SNPs) and PCa progression. METHODS: A keyword search was performed in Pubmed, EMBASE, Scopus, Web of Science, and Cochrane for publications between 2007 and 2022. We included articles with adjusted and significant associations, a median follow-up greater than or equal to 24 months, patients taken to radical prostatectomy (RP) as a first therapeutic option, and results presented based on biochemical recurrence (BCR). RESULTS: In the 27 articles selected, 73 SNPs were identified in 39 genes, organized in seven functional groups. Of these, 50 and 23 SNPs were significantly associated with a higher and lower risk of PCa progression, respectively. Likewise, four haplotypes were found to have a significant association with PCa progression. CONCLUSION: This article highlights the importance of SNPs as potential markers of PCa progression and their possible functional relationship with some genes relevant to its development and progression. However, most variants were identified only in cohorts from two countries; no additional studies reproduce these findings.

Stabilization of Diborynes versus Destabilization of Diborenes by Coordination of Lewis Bases: Unravelling the Dichotomy.

We have quantum chemically investigated the boron-boron bonds in B2 , diborynes B2 L2 , and diborenes B2 H2 L2 (L=none, OH2 , NH3 ) using dispersion-corrected relativistic density functional theory at ZORA-BLYP-D3(BJ)/TZ2P. B2 has effectively a single B-B bond provided by two half π bonds, whereas B2 H2 has effectively a double B=B bond provided by two half π bonds and one σ 2p-2p bond. This different electronic structure causes B2 and B2 H2 to react differently to the addition of ligands. Thus, in B2 L2 , electron-donating ligands shorten and strengthen the boron-boron bond whereas, in B2 H2 L2 , they lengthen and weaken the boron-boron bond. The aforementioned variations in boron-boron bond length and strength become more pronounced as the Lewis basicity of the ligands L increases.

Tobramycin Systemic Absorption in Lung Transplant Recipients Treated With Inhaled Tobramycin: A Cohort Study.

Inhaled tobramycin treatment has been associated with nephrotoxicity in some case reports, but limited data are available about serum levels and its possible systemic absorption in lung transplant recipients (LTR). We conducted a single-center, observational and retrospective study of all adult (>18 years old) LTR treated with inhaled tobramycin for at least 3 days between June 2019 and February 2022. Trough serum levels were collected and >2 µg/mL was considered a high drug level. The primary outcome assessed the presence of detectable trough levels, while the secondary outcome focused on the occurrence of acute kidney injury (AKI) in individuals with detectable trough levels. Thirty-four patients, with a median age of 60 years, were enrolled. The primary indications for treatment were donor bronchial aspirate bacterial isolation (18 patients) and tracheobronchitis (15 patients). In total, 28 patients (82%) exhibited detectable serum levels, with 9 (26%) presenting high levels (>2 µg/mL). Furthermore, 9 patients (26%) developed acute kidney injury during the treatment course. Median trough tobramycin levels were significantly elevated in invasively mechanically ventilated patients compared to non-ventilated individuals (2.5 µg/mL vs. 0.48 µg/mL) (p < 0.001). Inhaled tobramycin administration in LTRs, particularly in those requiring invasive mechanical ventilation, may result in substantial systemic absorption.

Frontline perspectives on barriers to care for patients with California Medicaid: a qualitative study.

BACKGROUND: While insurance is integral for accessing healthcare in the US, coverage alone may not ensure access, especially for those publicly insured. Access barriers for Medicaid-insured patients are rooted in social drivers of health, insurance complexities in the setting of managed care plans, and federal- and state-level policies. Elucidating barriers at the health system level may reveal opportunities for sustainable solutions. METHODS: To understand barriers to ambulatory care access for patients with Medi-Cal (California's Medicaid program) and identify improvement opportunities, we performed a qualitative study using semi-structured interviews of a referred sample of clinicians and administrative staff members experienced with clinical patient encounters and/or completion of referral processes for patients with Medi-Cal (n = 19) at a large academic medical center. The interview guide covered the four process steps to accessing care within the health system: (1) scheduling, (2) referral and authorization, (3) contracting, and (4) the clinical encounter. We transcribed and inductively coded the interviews, then organized themes across the four steps to identify perceptions of barriers to access and improvement opportunities for ambulatory care for patients with Medi-Cal. RESULTS: Clinicians and administrative staff members at a large academic medical center revealed barriers to ambulatory care access for Medi-Cal insured patients, including lack of awareness of system-level policy, complexities surrounding insurance contracting, limited resources for social support, and poor dissemination of information to patients. Particularly, interviews revealed how managed Medi-Cal impacts academic health systems through additional time and effort by frontline staff to facilitate patient access compared to fee-for-service Medi-Cal. Interviewees reported that this resulted in patient care delays, suboptimal care coordination, and care fragmentation. CONCLUSIONS: Our findings highlight gaps in system-level policy, inconsistencies in pursuing insurance authorizations, limited resources for scheduling and social work support, and poor dissemination of information to and between providers and patients, which limit access to care at an academic medical center for Medi-Cal insured patients. Many interviewees additionally shared the moral injury that they experienced as they witnessed patient care delays in the absence of system-level structures to address these barriers. Reform at the state, insurance organization, and institutional levels is necessary to form solutions within Medi-Cal innovation efforts.

Effect of temperature on the gas-phase reaction of CH3CN with OH radicals: experimental (T = 11.7-177.5 K) and computational (T = 10-400 K) kinetic study.

Acetonitrile (CH3CN) is present in the interstellar medium (ISM) in a variety of environments. However, at the ultracold temperatures of the ISM, radical-molecule reactions are not widely investigated because of the experimental handicap of getting organic molecules in the gas phase by conventional techniques. The CRESU (French acronym for Reaction Kinetics in a Uniform Supersonic Flow) technique solves this problem. For this reason, we present in this work the kinetic study of the gas-phase reaction of CH3CN with one of the most ubiquitous radicals, the hydroxyl (OH) radical, as a function of temperature (11.7-177.5 K). The kinetic technique employed to investigate the CH3CN + OH reaction was the pulsed laser photolysis-laser induced fluorescence. The rate coefficient for this reaction k(T) has been observed to drastically increase from 177.5 K to 107.0 K (about 2 orders of magnitude), while the increase in k(T) from 107.0 K to 11.7 K was milder (around 4 times). The temperature dependent expressions for k(T) are provided in the two distinct T-ranges, excluding the upper limit obtained for k(177.5 K): In addition, the rate coefficients estimated by the canonical competitive unified statistical (CCUS) theory show a similar behaviour to the experimental results, when evaluated within the high-pressure limit. This is consistent with the experimentally observed independence of k(T) with total gas density at selected temperatures. Astrochemical networks, such as the KIDA database or UMIST, do not include the CH3CN + OH reaction as a potential depletion process for acetonitrile in the ISM because the current studies predict very low rate coefficients at IS temperatures. According to the model (T = 10 K), the impact of the titled reaction on the abundances of CH3CN appears to be negligible in dark molecular clouds of the ISM (∼1% of the total depletion reactions included in UMIST network). With respect to the potential formation of the CH2CN radical in those environments, even in the most favourable scenario, where this radical could be formed in a 100% yield from the CH3CN + OH reaction, this route would only contribute around 2% to the current assumed formation routes by the UMIST network.

Evaluating silicosis risk: Assessing dust constitution and influence of water as a primary prevention measure in cutting and polishing of silica agglomerates, granite and marble.

An increasing number of silicosis cases have been reported related to the use of silica agglomerates. Many studies agree on the severity of this disease, which often presents with severe clinical forms in young workers and after a short latency period. Are there differences in the composition of dust generated by cutting and polishing with silica agglomerates versus granite and marble? Does the use of water injection reduce the risk associated with the use of these materials? We carried out a comparative observational-analytical study, measuring the concentration of dust generated during different machining operations on three different materials: granite, marble, and silica agglomerates. The effect of water injection on dust generation was evaluated. Personal sampling pumps were used, connected to a cyclone with polyvinyl chloride filters. The flow rate of the pumps was adjusted using a piston flowmeter. Measurements with a cascade impactor were made to assess the size distribution of respirable crystalline silica particles within the respirable fraction. In addition, environmental measurements with a spectrometer were made. 10 tests were carried out on granite and silica agglomerates for each procedure. In the case of marble, with very low silica content, only 2 tests of each type were carried out. Duration of each measurement was between 6 and 25 min. Cleaning times were set for each of the operations. The amount of dust collected in the respirable fraction was 70.85, 32.50 and 35.78 mg/m3 for dry cutting; 6.50, 3.75 and 3.95 mg/m3 for wet cutting; and 21.35, 13.68 and 17.50 mg/m3 for dry polishing, for granite, marble, and silica agglomerates respectively. Dry procedures in marble, silica agglomerates and granite showed higher dust concentration of particles smaller than 0.5 µm. Silica agglomerates showed higher concentrations of respirable crystalline silica particles than granite and marble, mainly with dry procedures. The greater production of small particles in dry and wet procedures with silica agglomerates shows that water injection is an insufficient preventive measure.

Post Cardiac Arrest Care in the Cardiac Intensive Care Unit.

PURPOSE OF REVIEW: Cardiac arrests constitute a leading cause of mortality in the adult population and cardiologists are often tasked with the management of patients following cardiac arrest either as a consultant or primary provider in the cardiac intensive care unit. Familiarity with evidence-based practice for post-cardiac arrest care is a requisite for optimizing outcomes in this highly morbid group. This review will highlight important concepts necessary to managing these patients. RECENT FINDINGS: Emerging evidence has further elucidated optimal care of post-arrest patients including timing for routine coronary angiography, utility of therapeutic hypothermia, permissive hypercapnia, and empiric aspiration pneumonia treatment. The complicated state of multi-organ failure following cardiac arrest needs to be carefully optimized by the clinician to prevent further neurologic injury and promote systemic recovery. Future studies should be aimed at understanding if these findings extend to specific patient populations, especially those at the highest risk for poor outcomes.

Spontaneous Remission of Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report.

Spontaneous remissions (SRs) in blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are infrequent, poorly documented, and transient. We report a 40-year-old man presenting with bycitopenia and soft tissue infection. The bone marrow exhibited 3% abnormal cells. Immunophenotyping of these cells revealed the antigens CD45+ (dim), CD34+, CD117+, CD123+ (bright), HLA-DR+ (bimodal), CD56+ (bright), CD33+, CD13+, CD2+, and CD22+ (dim) and the partial expression of the CD10+, CD36+, and CD7+ antigens. All other myeloid, monocytic, and lymphoid antigens were negative. Genetic studies showed a complex karyotype and mutations in the TP53R337C and KRASG12D genes. On hospital admission, the patient showed a subcutaneous nodule on the right hand and left lower limb. Flow cytometry multiparameter (FCM) analysis showed the presence of 29% abnormal cells with the previously described immunophenotype. The patient was diagnosed with BPDCN. The patient was treated with broad-spectrum antibiotics for soft tissue infection, which delayed therapy for BPDCN. No steroids or chemotherapeutic or hypomethylating agents were administered. His blood cell counts improved and skin lesions disappeared, until the patient relapsed five months after achieving spontaneous remission. About 60% of abnormal cells were identified. No changes in immunophenotype or the results of genetic studies were observed. The patient underwent a HyperCVAD chemotherapy regimen for six cycles. Consolidation therapy was performed via allogeneic bone marrow transplantation with an HLA-unrelated donor. One year after the bone marrow transplant, the patient died due to the progression of his underlying disease, coinciding with a respiratory infection caused by SARS-CoV-2. In the available literature, SRs are often linked to infections or other stimulators of the immune system, suggesting that powerful immune activation could play a role in controlling the leukemic clone. Nevertheless, the underlying mechanism of this phenomenon is not clearly understood. We hypothesize that the immune system would force the leukemic stem cell (LSC) to undergo a state of quiescence. This loss of replication causes the LSC progeny to die off, resulting in the SR of BPDCN.

TCP15 interacts with GOLDEN2-LIKE 1 to control cotyledon opening in Arabidopsis.

After germination, exposure to light promotes the opening and expansion of the cotyledons and the development of the photosynthetic apparatus in a process called de-etiolation. This process is crucial for seedling establishment and photoautotrophic growth. TEOSINTE BRANCHED 1, CYCLOIDEA, and PROLIFERATING CELL FACTORS (TCP) transcription factors are important developmental regulators of plant responses to internal and external signals that are grouped into two main classes. In this study, we identified GOLDEN2-LIKE 1 (GLK1), a key transcriptional regulator of photomorphogenesis, as a protein partner of class I TCPs during light-induced cotyledon opening and expansion in Arabidopsis. The class I TCP TCP15 and GLK1 are mutually required for cotyledon opening and the induction of SAUR and EXPANSIN genes, involved in cell expansion. TCP15 also participates in the expression of photosynthesis-associated genes regulated by GLK1, like LHCB1.4 and LHCB2.2. Furthermore, GLK1 and TCP15 bind to the same promoter regions of different target genes containing either GLK or TCP binding motifs and binding of TCP15 is affected in a GLK1-deficient background, suggesting that a complex between TCP15 and GLK1 participates in the induction of these genes. We postulate that GLK1 helps to recruit TCP15 for the modulation of cell expansion genes in cotyledons and that the functional interaction between these transcription factors may serve to coordinate the expression of cell expansion genes with that of genes involved in the development of the photosynthetic apparatus.

Effects of chaotropic salts on global proteome stability in halophilic archaea: Implications for life signatures on Mars.

Halophilic archaea thriving in hypersaline environments, such as salt lakes, offer models for putative life in extraterrestrial brines such as those found on Mars. However, little is known about the effect of the chaotropic salts that could be found in such brines, such as MgCl2 , CaCl2 and (per)chlorate salts, on complex biological samples like cell lysates which could be expected to be more representative of biomarkers left behind putative extraterrestrial life forms. We used intrinsic fluorescence to study the salt dependence of proteomes extracted from five halophilic strains: Haloarcula marismortui, Halobacterium salinarum, Haloferax mediterranei, Halorubrum sodomense and Haloferax volcanii. These strains were isolated from Earth environments with different salt compositions. Among the five strains that were analysed, H. mediterranei stood out as a results of its high dependency on NaCl for its proteome stabilization. Interestingly, the results showed contrasting denaturation responses of the proteomes to chaotropic salts. In particular, the proteomes of strains that are most dependent or tolerant on MgCl2 for growth exhibited higher tolerance towards chaotropic salts that are abundant in terrestrial and Martian brines. These experiments bridge together global protein properties and environmental adaptation and help guide the search for protein-like biomarkers in extraterrestrial briny environments.

Melanocortin 1 receptor variants and their association with phenotypic characteristics and sporadic multiple primary melanomas in a cohort of 402 Spanish subjects.

The melanocortin 1 receptor (MC1R) gene is considered to be a major determinant of the risk of melanoma. The role of MC1R polymorphisms as predisposing factors for the development of a second primary melanoma is not well established. The present study analyses the characteristics from subjects with certain MC1R variants without any other genetic predisposition, as well as the risk of second primary melanoma associated with these variants. We performed a prospective longitudinal single-centre study based on follow-up information of 402 patients diagnosed with cutaneous melanoma. MC1R gene was sequenced in all subjects. High-risk variants were defined as those previously associated with melanoma (V60L, V92M, I155T, R160W, R163Q and D294H). 253 (63%) patients had at least one predisposing variant. These individuals had higher proportion of red/blonde hair, multiple primary melanomas and first melanoma diagnosis under the age of 60. Second primary melanomas were detected in 28 (3.8%) subjects. Having more than 25 melanocytic nevi was associated significantly to the development of second primary melanomas. A higher proportion of individuals carrying at least one predisposing MC1R variant develop a second melanoma, although statistical significance was not reached. Therefore, some MC1R polymorphisms might determine clinical and histological differences between patients with cutaneous melanoma and may represent a risk factor for second primary melanoma, although more studies are needed.

Human monkeypox virus in a tertiary hospital in Madrid, Spain: An observational study of the clinical and epidemiological characteristics of 53 cases.

A new outbreak of monkeypox virus (MPXV) infection, a zoonotic infection endemic in Central and West Africa, is spreading throughout the world with new epidemiology and clinical features. Our aim was to characterize patients presenting to Dermatology emergency room with a MPXV infection between 15 May and 30 June 2022 in a tertiary hospital in Madrid, Spain. We collected 53 patients and describe their clinical, demographic and epidemiological characteristics and followed their evolution. Most of the patients were men who had sex with men with high-risk sexual practices and no recent travels abroad. Most of them (91%) had had a sexually transmitted infection before. All patients had typical skin lesions consisting of vesicular-pustular rash with central umbilication which was localized or disseminated. The most frequent extracutaneous symptoms were fever, painful regional lymphadenopathy and asthenia. Proctitis was present in more than one third of patients. All patients were diagnosed by real time polymerase chain reaction of samples obtained from skin lesions. Pharyngeal and/or rectal exudates demonstrated MPXV in 74% of patients. The current worldwide outbreak of MPXV infections shows epidemiological and clinical differences from previous ones. Clinicians should be aware of these characteristics to correctly diagnose this emerging disease.

Who Will Have a Second Melanoma? A Prospective Longitudinal Study in Patients without Any Genetic Predisposition.

BACKGROUND: Melanoma patients have a higher risk of developing additional melanomas. Predisposing factors of a second primary melanoma in patients without any genetic predisposition are not well established. OBJECTIVES: The aim of this study was to identify risk factors related to the development of a second primary melanoma in order to know which patients should be followed up closely. METHODS: A longitudinal study was performed at Hospital Gregorio Marañón (Madrid, Spain), based on follow-up data of patients diagnosed with cutaneous melanoma from 1998 to 2020. RESULTS: After a median follow-up of 82 months, 58 out of 1523 (3.8%) patients developed a second melanoma. In 11 patients (19%), a second melanoma was diagnosed more than 10 years after their first melanoma. Second melanomas more commonly had a lower mean tumour thickness than the first ones, but 8 out of 58 (13.8%) had a higher tumour thickness than their first melanoma. Skin phototype I-II, having more than 50 melanocytic nevi, and recurrent sunburns were associated with the development of a second melanoma. In multivariate analysis, skin phototype I-II (odds ratio [OR] = 5.41; p < 0.001) and a higher number of nevi (OR = 3.44; p < 0.001) remained as independent risk factors for the development of a second melanoma. CONCLUSIONS: Patients with fair skin phototype and more than 50 melanocytic nevi are at increased risk of developing a second primary melanoma and should be closely monitored throughout their lives to detect earlier additional melanomas.

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19. Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, Setting, and Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Interventions: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main Outcomes and Measures: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Results: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Conclusions and Relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

Physiological Roles and Mechanisms of Action of Class I TCP Transcription Factors.

TEOSINTE BRANCHED1, CYCLOIDEA, PROLIFERATING CELL FACTOR 1 and 2 (TCP) proteins constitute a plant-specific transcription factors family exerting effects on multiple aspects of plant development, such as germination, embryogenesis, leaf and flower morphogenesis, and pollen development, through the recruitment of other factors and the modulation of different hormonal pathways. They are divided into two main classes, I and II. This review focuses on the function and regulation of class I TCP proteins (TCPs). We describe the role of class I TCPs in cell growth and proliferation and summarize recent progresses in understanding the function of class I TCPs in diverse developmental processes, defense, and abiotic stress responses. In addition, their function in redox signaling and the interplay between class I TCPs and proteins involved in immunity and transcriptional and posttranslational regulation is discussed.

Adipose Tissue, Non-Communicable Diseases, and Physical Exercise: An Imperfect Triangle.

The study of adipose tissue has received considerable attention due to its importance not just in maintaining body energy homeostasis but also in playing a role in a number of other physiological processes. Beyond storing energy, adipose tissue is important in endocrine, immunological, and neuromodulatory functions, secreting hormones that participate in the regulation of energy homeostasis. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favoring the secretion of deleterious adipocytokines that induce a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases and even some types of cancer. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity, with emphasis on hypocaloric diets and exercise. The aim of this review is to examine the pathophysiological mechanisms of obesity, considering the relationship among adipose tissue and two aspects that contribute positively or negatively to keeping a healthy body homeostasis, namely, exercise and noninfectious diseases. We conclude that the relationship of these aspects does not have homogeneous effects among individuals. Nevertheless, it is possible to establish some common mechanisms, like a decrease in pro-inflammatory markers in the case of exercise, and an increase in chronic inflammation in non-communicable diseases. An accurate diagnosis might consider the particular variables of a patient, namely their molecular profile and how it affects its metabolism, routines, and lifestyle; their underling health conditions; and probably even the constitution of their microbiome. We foresee that the development and accessibility of omics approaches and precision medicine will greatly improve the diagnosis, treatment, and successful outcomes for obese patients.

A systematic review and evaluation of post-stroke depression clinical practice guidelines.

OBJECTIVE: Post-stroke depression is a depressive mood disorder that follows a cerebrovascular accident and is a burden on stroke patients. Its management is included in clinical practice guidelines focused on stroke, and the recommended treatment is selective serotonin reuptake inhibitors in conjunction with psychotherapy. Clinical practice guidelines are recommendations used to standardize best medical practice, but there is no current evaluation of guidelines containing post stroke depression recommendations. Thus, the objective is to appraise the selected guidelines manner of development and quality. MATERIALS AND METHODS: A systematic literature review across three databases and a manual google search was performed to collect guidelines that included recommendations on the management of post-stroke depression. 1236 guidelines were screened, and 27 were considered for inclusion. Considered guidelines were manually reviewed by the authors, and ultimately, 7 met inclusion criteria. The appraisal of guidelines for research and evaluation was used to evaluate these guidelines' recommendations around post-stroke depression. RESULTS: Three guidelines met the threshold considered "High", with all of them having five or more quality domains eclipse the cutoff score of 70%. Across all guidelines, the highest scoring domains were "Scope and Purpose", "Clarity of Presentation", and "Editorial Independence" with scores of 76.98%, 73.81%, and 91.36% respectively. The lowest scoring domains were "Applicability", "Rigor of Development", and "Stakeholder Involvement" with respective scores of 58.73%, 54.02%, and 43.90%. CONCLUSIONS: The domains "Applicability", "Rigor of Development," and "Stakeholder Involvement" were the lowest scoring domains. These specific domains represent areas in which future guidelines could be more developed.

Identification of seasonal variation in the diagnosis of acute myeloid leukaemia: a population-based study.

Until now, the role that seasonal factors play in the aetiology of acute myeloid leukaemia (AML) has been unclear. Demonstration of seasonality in AML diagnosis would provide supportive evidence of an underlying seasonal aetiology. To investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age, we used population-based data from a Spanish hospital discharge registry. We conducted a larger study than any to date of 26 472 cases of AML diagnosed in Spain between 2004 and 2015. Using multivariable Poisson generalized linear autoregressive moving average modelling, we found an upward long-term trend, with monthly incidence rates of AML annually increasing by 0.4% [95% confidence interval (CI), 0.2%-0.6%; p = 0.0011]. January displayed the highest incidence rate of AML, with a minimum average difference of 7% when compared to February (95% CI, 2%-12%; p = 0.0143) and a maximum average difference of 16% compared to November (95% CI, 11%-21%; p < 0.0001) and August (95% CI, 10%-21%; p < 0.0001). Such seasonal effect was consistent among subgroups according to sex and age. Our finding that AML diagnosis is seasonal strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development and/or proliferation of disease, pointing to prevention opportunities.