Wunderlich syndrome as a rare complication of polyarteritis nodosa: a case report.

Spontaneous subcapsular and perirenal hemorrhage, known as Wunderlich syndrome (WS), is a rare clinical manifestation of polyarteritis nodosa (PAN). We report a case of a 48-year-old male with a history of recurrent episodes of leg muscle tenderness and dysesthesia, bilateral flank pain, painful nodular skin lesions in the lower limbs, weight loss, and difficult-to-control arterial hypertension. The abdominopelvic computed tomography angiography showed a large left perirenal hematoma, leading to the patient's admission to the intensive care unit. After the exclusion of infectious or neoplastic foci, the patient was diagnosed with PAN and started intravenous methylprednisolone pulses with a good response. Since WS is a rare initial clinical manifestation of PAN, an early diagnosis and aggressive treatment will significantly improve clinical outcomes.

Recruitment and mortality of Rhizophora mangle L. seedlings in the Tropical Southwestern Atlantic mangrove.

Studies in the long-term recruitment and mortality of mangrove seedlings can help to understand mangrove demography and its relationship with climatic variables, environmental restoration and advances in the ecology of this ecosystem. A seven-year population dynamics study of seedling recruitment and mortality in cohorts of Rhizophora mangle L. was carried out to identify expansion processes and patterns of survival in the understory of mangrove forests on the Atlantic coast of Brazil. The present study aimed to evaluate the relationship between recruitment and mortality R. mangle seedlings at the population level, salinity, and climatic variables (precipitation, temperature and humidity). On an annual scale, seedling recruitment was positively correlated with mean temperature. Seedling density was negatively correlated with the number of recruits and positively with the number of deaths. The number of recruits was associated with dead seedlings, temperature and precipitation considering a population scale, without grouping the data. The seedling density in the stands increased with the number of dead seedlings. Our findings described the relationship between climate variability (durability and magnitude of the dry/rainy season) and the long-term population dynamics of R. mangle seedlings in a poorly studied region and from what moment, on a monthly and annual time scale, did this relationship become significant and changes occur. The findings of this study provide information on the population dynamics of the species that will help in understanding mangrove demography. These results have important implications for projections about the recruitment and survival of the species thinking about to long-term climate change that will modify current weather patterns and mangrove conservation efforts.

Emollients in dermatological creams: Early evaluation for tailoring formulation and therapeutic performance.

The targeted choice of the emollient of a cream determines its physicochemical properties and clinical effectiveness. This work researched the effects of emollient properties on the final characteristics and potential performance of oil-in-water dermatological creams. Seven emollients with different chemical characteristics and structures (alkane, triglyceride, ether, silicone, vegetable oils, and mineral oil) were tested in a model formulation. Early stability, pH, droplet size distribution, rheology, tackiness, adhesivity, spreadability, tribology, and release profile of a lipophilic substance model (in Franz cells, through a synthetic membrane, for six hours) were assessed. The creams had acid epicutaneous pH and a "shear-thinning" "solid-like" viscoelastic behavior. Among the seven emollients' properties, polarity, density, and viscosity were the most influential. Droplet parameters were the most impacted, pH and release were moderately affected, and the textural properties were lowly to moderately impacted. The emollient substitution in the model formulation affected the experimental parameters differently, allowing formulation optimization and tailoring its potential therapeutic performance regarding drug release, coadjutant effects, and dwell time on the skin. By looking at the creams' characteristics, it was possible to select the best-suited emollients for releasing a lipophilic drug, applying on painful skin, and formulation in wash-off products or leave-on protective barrier creams.

Validation of a hematology analyzer in donkey medicine.

Asinina de Miranda is a protected donkey sub-species from the Mirandês plateau in northeastern of Portugal. Donkeys are animals that have substantially lost their place as working animals in modern society, this had led to a decrease in their population numbers. A need to preserve native species has led to the foundation of organizations like Associação para o Estudo e Proteção do Gado Asinino (AEPGA) and the development of studies regarding breed welfare, such as hematology. The IDEXX ProCyte Dx is a veterinary hematology analyzer validated for several species, but not for donkeys. The aim of this study was to validate the ProCyte Dx for Asinina de Miranda donkeys. The validation requires a controlled study of precision, carryover, linearity and comparison between the equipment and the manually obtained values for the leukocyte differential count and hematocrit. Results indicated coefficient of variation was good (below 5 %) for both the intra-assay and the inter-assay precision, except for basophils. Carryover was 0 % for all the parameters except platelets (5.88 %). Linearity showed a very high Pearson correlation coefficient, above 0.99, for erythrocytes, hematocrit, hemoglobin, leucocytes, neutrophils, lymphocytes, monocytes, eosinophils, platelets and plateletcrit. Comparison demonstrated excellent agreement for hematocrit (rs=0.96) and good Spearman rank correlation for neutrophils (rs=0.84) and lymphocytes (rs=0.90). Accuracy for total leukocyte count and platelets could not be determined. In conclusion, the ProCyte Dx seems appropriate to be used in Asinina de Miranda hematology.

Antimicrobial resistance expansion in pathogens: a review of current mitigation strategies and advances towards innovative therapy.

The escalating problem of antimicrobial resistance (AMR) proliferation in clinically important pathogens has become one of the biggest threats to human health and the global economy. Previous studies have estimated AMR-associated deaths and disability-adjusted life-years (DALYs) in many countries with a view to presenting a clearer picture of the global burden of AMR-related diseases. Recently, several novel strategies have been advanced to combat resistance spread. These include efflux activity inhibition, closing of mutant selection window (MSW), biofilm disruption, lytic bacteriophage particles, nanoantibiotics, engineered antimicrobial peptides, and the CRISPR-Cas9 gene-editing technique. The single or integrated deployment of these strategies has shown potentialities towards mitigating resistance and contributing to valuable therapeutic outcomes. Correspondingly, the new paradigm of personalized medicine demands innovative interventions such as improved and accurate point-of-care diagnosis and treatment to curtail AMR. The CRISPR-Cas system is a novel and highly promising nucleic acid detection and manipulating technology with the potential for application in the control of AMR. This review thus considers the specifics of some of the AMR-mitigating strategies, while noting their drawbacks, and discusses the advances in the CRISPR-based technology as an important point-of-care tool for tracking and curbing AMR in our fight against a looming 'post-antibiotic' era.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis recurrence temporally associated with allergen-specific immunotherapy in a female adolescent: a case report.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in pediatric patients. It is clinically characterized by fever flares lasting 3-7 days, reappearing every 2-8 weeks with a distinctive clockwork regularity. PFAPA generally begins before 5 years of age and usually ceases 3-5 years after onset. Recurrences may be observed in adolescence and adulthood in up to 20% of cases. The authors aim to describe a case of PFAPA recurrence in adolescence temporally associated with allergen-specific immunotherapy (ASIT). A 16-year-old female patient was referred to the rheumatology unit due to recurrent episodes of fever one month after initiating ASIT for allergic rhinitis. These episodes occurred every 4 weeks and lasted 3 days. During these episodes, she also presented with a sore throat, tonsillar exudates, and cervical lymphadenopathy. Abortive treatment with oral prednisolone was attempted in these episodes, with complete resolution of fever after a single dose. After reviewing her medical background, she had previously experienced febrile episodes accompanied by aphthous ulcers and tonsillar exudates occurring every 7-8 weeks from age 2-7. The etiopathogenesis of PFAPA remains uncertain. Environmental triggers, particularly those with immunomodulator effects, may interfere with the immune responses responsible for PFAPA occurrence, but the mechanisms are still unclear. The authors describe the first report of the reappearance of PFAPA flares, possibly due to ASIT. Further studies are needed to fully clarify if ASIT constitutes a true environmental trigger of PFAPA.

Agronomic parameters of sugarcane under planting densities in different cultivation cycles.

Low density sugarcane plantation (LDSP) has been implemented by some sugarcane producers in Brazil, aiming to save seeds and operational costs. The study was carried out in the municipality of Areia, Paraíba, Brazil. Five planting densities were used, varying from 5 to 25 m-2 of buds arranged in randomized blocks, with four replications. Data were measured annually over three cultivation cycles (2017 to 2020), during which the field was fertilized with NPK and the harvests were carried out manually without prior burning. The lower planting density presents higher productivity only in the cane plant (101.03 t ha-1) due to the higher plant height (2.37 m) and the higher number of stalks (11 stalks m-2), suggesting that these variables are due to the greater availability of light, water and photosynthate. However, there is a drastic reduction in sugarcane yield for this lower population in the 2nd ratoon by up to 65.62%, which is correlated with number of stalks per meter. We demonstrate the agronomic viability of LDSP in the population of 10 buds m-2 in relation to conventional planting of sugarcane until the 2nd ratoon. Data are important for future studies to present additional considerations for other production factors, such as the effects of mechanized harvesting and the management of nutrients and water, assessing the sustainability of this large-scale planting system.

Motor Reaction Time, Sarcopenia and Functional Skills in Elderly Women: A Cross-Sectional Study.

IMPORTANCE: Aging generates changes over the years. Because of this, the musculoskeletal system is directly degraded and suffer deficits in its performance in elderly patients with Sarcopenia, as this condition is characterized by a decrease in muscle mass and function. OBJECTIVE: Correlate the motor reaction time and functional skills of non-sarcopenic, pre-sarcopenic and sarcopenic elderly women, and analyze influence on the risk of falls. DESIGN: Cross-sectional observational analytical study, following the methodological strategies of STROBE (Strengthening the Reporting of Observational Studies in Epidemiology), carried out under the approval of the Research Ethics Committee of the Unievangélica University, no. 3.694.235/2019. SETTING: Participants were evaluated regarding: cognitive status, level of physical activity, fear of falling, body composition, motor reaction time, static and dynamic balance, gait kinetics, strength and endurance of the lower limbs and finally handgrip strength. PARTICIPANTS: A total of 59 volunteer elderly women were assessed following the diagnostic criteria for sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). RESULTS: The results show that there was a greater difference in motor reaction time between the non-sarcopenic and sarcopenic elderly women due to the executing organ being damaged by the presence of sarcopenia, causing motor response to slowdown. Functional deficit, fear of falling and greater risk of falls were observed in the sarcopenic group, under the harmful influence of increased motor reaction time. CONCLUSION: Sarcopenic elderly women present increased motor reaction time, that is, slowed motor responses due to decreased muscle mass, strength and impaired musculature, which generate functional deficits that contribute to an increased risk of falls.

Dietary phytate induces subclinical mechanical allodynia in mice.

Neuropathic pain is a condition with varying origins, including reduced dietary micronutrient intake. Phytate is a polyphosphate found in seeds and grains that can act as an antinutrient due to the ability of sequester essential divalent metals. Here we tested whether moderate dietary phytate intake could alter nociceptive pain. We subjected weaning mice to a chow supplemented with 1% phytate for eight weeks. Body weight gain, glycemic responses, food ingestion, water ingestion, and liver and adipose tissue weights were not altered compared to controls. We observed a decreased mechanical allodynia threshold in the intervention group, although there were no changes in heat- or cold-induced pain. Animals consuming phytate showed reduced spinal cord tumor necrosis factor (TNF), indicating altered inflammatory process. These data provide evidence for a subclinical induction of mechanical allodynia that is independent of phytate consumption in animals with otherwise normal phenotypic pattern.

Predictors of mortality in critically ill patients with COVID-19 and diabetes.

The COVID-19 pandemic has challenged the entire world, and patients with diabetes mellitus (DM) have been particularly affected. We aimed to evaluate predictors of mortality during the first 30 days of hospitalization in critically ill patients with COVID-19 and comorbid DM. This prospective study included 110 critically ill patients admitted with COVID-19 infection. Thirty-two (29%) patients had a previous diagnosis of DM. Clinical variables, laboratory tests, and vascular biomarkers, such as VCAM-1, syndecan-1, ICAM-1, angiopoietin-1, and angiopoeitin-2, were evaluated after intensive care unit (ICU) admission. A comparison was made between patients with and without DM. No difference in mortality was observed between the groups (48.7 vs 46.9%, P=0.861). In the multivariate Cox regression analysis, VCAM-1 levels at ICU admission (HR: 1 [1-1.001], P<0.006) were associated with death in patients with DM. Among patients with DM, advanced age (HR 1.063 [1.031-1.096], P<0.001), increased Ang-2/Ang-1 ratio (HR: 4.515 [1.803-11.308] P=0.001), and need for dialysis (HR: 3.489 [1.409-8.642], P=0.007) were independent predictors of death. Higher levels of VCAM-1 in patients with DM was better at predicting death of patients with severe COVID-19 and comorbid DM, and their cut-off values were useful for stratifying patients with a worse prognosis. Vascular biomarkers VCAM-1 and Ang-2/Ang-1 ratio were predictors of death in patients with severe COVID-19 and comorbid DM and those without DM. Additionally, kidney injury was associated with an increased risk of death.

Isolation and genotypic characterization of extended-spectrum beta-lactamase-producing Escherichia coli O157:H7 and Aeromonas hydrophila from selected freshwater sources in Southwest Nigeria.

The proliferation of antibiotic-resistant bacteria and antimicrobial resistance is a pressing public health challenge because of their possible transfer to humans via contact with polluted water sources. In this study, three freshwater resources were assessed for important physicochemical characteristics as well as heterotrophic and coliform bacteria and as potential reservoirs for extended-spectrum beta-lactamase (ESBL) strains. The physicochemical characteristics ranged from 7.0 to 8.3; 25 to 30 °C, 0.4 to 93 mg/L, 0.53 to 8.80 mg/L and 53 to 240 mg/L for pH, temperature, dissolved oxygen (DO), biological oxygen demand (BOD5) and total dissolved solids, respectively. The physicochemical characteristics mostly align with guidelines except for the DO and BOD5 in some instances. Seventy-six (76) Aeromonas hydrophila and 65 Escherichia coli O157: H7 isolates were identified by preliminary biochemical analysis and PCR from the three sites. Among these, A. hydrophila displayed higher frequencies of antimicrobial resistance, with all 76 (100%) isolates completely resistant to cefuroxime and cefotaxime and with MARI ≥ 0.61. The test isolates showed more than 80% resistance against five of the ten test antimicrobials, with resistance against cefixime, a cephalosporin antibiotic being the highest at 95% (134/141). The frequency of the detection of the resistance genes in the A. hydrophila isolates generally ranged between 0% (blaSHV) and 26.3% (blaCTX-M), while the frequency of detection among the E. coli O157:H7 isolates ranged between 4.6% (blaCTX-M) and 58.4% (blaTEM). Our findings indicate that the distribution of antibiotic-resistant bacteria with diverse ESBL-producing capabilities and virulence genes in freshwater sources potentially threatens public health and the environment.

Uveitis in patients with oligoarticular juvenile idiopathic arthritis and juvenile spondyloarthritis/enthesitis related arthritis: is there any difference?

Juvenile idiopathic arthritis (JIA) is the most common systemic disease causing uveitis in childhood and adolescence.

Butyrate supplementation in the liquid diet of dairy calves leads to a rapid recovery from diarrhea and reduces its occurrence and relapses in the preweaning period.

The present study aimed to evaluate the effect of continuous butyrate administration in dairy calves' liquid diet considering diarrhea, metabolic profile, gastrointestinal development, and corporal growth. Immediately after birth, calves were randomly allocated into 2 groups of 62 calves (50 females and 12 males), with access to water and a solid feed ad libitum. The butyrate group (BG) received 4 g/d of sodium butyrate (Admix Easy, Adisseo) diluted in the whole milk, and the control group (CG) received whole milk with no supplementation. Sodium butyrate was administered from d 1 of life until the weaning at 90 d. Feces consistency was assessed daily for the first 30 d of life and characterized by scores from 0 to 4 (0 and 1 for normal, and 2, 3, and 4 for abnormal feces). Diarrhea was diagnosed when the animals had abnormal feces and fever. Morbidity, recurrence, mortality, and lethality data were recorded and compared between the groups. Average daily gain (ADG) and corporal growth (body weight, thoracic perimeter, height at the withers, and croup width) were evaluated weekly, from the first day to d 30, and later at 45, 60, and 90 d of life. Blood samples were taken weekly for up to 30 d to determine the circulating levels of total calcium, phosphorus, chloride, bicarbonate, glucose, ß-hydroxybutyrate, and nonesterified fatty acids. The males were euthanized at 15 (n = 6 per group) and 30 d (n = 6 per group) for morphometric, histological, and gene expression analysis of the gastrointestinal tract. The results showed that the BG had a lower rate of morbidity (BG = 30% vs. CG = 50%) and recurrence (BG = 26.7% vs. CG = 60%) of diarrhea than the CG. In addition, the BG had abnormal feces for a shorter period (BG = 4.64 ± 0.47 d vs. CG = 8.6 ± 0.65 d). The ADG tended to be higher in BG than CG up to 30 and 60 d. Metabolic evaluations showed the lowest levels of glucose and highest levels of nonesterified fatty acids in BG. On d 30 of life, rumen papillae length, papilla area, duodenum villus length, and crypt depth were higher in BG than in CG. The duodenal gene expression at 30 d showed that animals with diarrhea episodes that did not receive butyrate had the highest levels of transcripts for the LCT and GLP2 genes. In addition, in different ways, both butyrate and neonatal diarrhea affected the gene expression of IGF1, SLC5A1, and AQP3. These results allow us to conclude that continuous supplementation with sodium butyrate improves gastrointestinal development, reduces the occurrence of diarrhea, and makes clinical conditions milder with faster recovery, favoring a higher ADG in the first 30 and 60 d of life. Based on these results, we conclude that sodium butyrate can be indicated for liquid diet supplementation to accelerate gastrointestinal tract development and prevent severe cases of neonatal diarrhea, tending to improve average daily gain until weaning.

Progressive proximal muscle weakness with subacute onset in an elderly patient: a case report. / Debilidad muscular proximal progresiva de inicio subagudo en un paciente anciano: descripción de un caso.

INTRODUCTION: Statins are some of the most widely prescribed medications. Although statins are generally well tolerated, they can lead to musculoskeletal side effects. Statin-induced necrotizing autoimmune myositis (SINAM) is a rare condition and the prevalence is only 1 per 100,000 people. This disorder is characterized by progressive and severe symmetric muscle weakness, marked elevation of creatine kinase and persistent symptoms despite statin discontinuation. Electromyography commonly shows a nonspecific irritable myopathy pattern indistinguishable from other inflammatory myopathies. Muscle biopsy shows the presence of necrotic fibers, regenerating fibers without significant inflammatory cells and diffuse or focal upregulation of major histocompatibility complex class I expression. The anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies represent a characteristic serological feature of SINAM. CASE REPORT: We present a patient who developed progressive muscle weakness after taking simvastatin for the last seven years. At initial presentation, her creatine kinase level was 2,954 U/L and anti-HMGCR antibodies were positive. The biopsy showed a profound myopathic features with numerous necrotic fibers, some regenerating fibers and perimysial inflammatory cell infiltrate, combined with a diffuse overexpression of major histocompatibility complex class I products. She was diagnosed with SINAM, statin was suspended and a high dose of systemic corticosteroids, intravenous immunoglobulin therapy and methotrexate was started. At three-month follow-up, she had significant improvement in muscle strength and creatine kinase level returned to normal. CONCLUSION: In this case, exclusion of inflammatory myopathies, metabolic muscle disorders and other neurological diseases is necessary for establishing a reliable diagnosis. In SINAM, simply discontinuing statin is often insufficient and aggressive immunosuppression or immunomodulation therapy is needed to achieve disease remission. This case aims to demonstrate that statins can induce serious muscular diseases that require aggressive immunosuppression.

TITLE: Debilidad muscular proximal progresiva de inicio subagudo en un paciente anciano: descripción de un caso.Introducción. Las estatinas son de los medicamentos más recetados. Aunque las estatinas generalmente se toleran bien, pueden provocar efectos secundarios musculoesqueléticos. La miopatía autoinmune necrotizante inducida por estatinas (SINAM) es una afección rara y la prevalencia sólo es de 1 de cada 100.000 personas. Este trastorno se caracteriza por debilidad muscular simétrica progresiva y grave, elevación marcada de la creatincinasa y síntomas persistentes a pesar de la interrupción de la estatina. La electromiografía suele mostrar un patrón de miopatía irritable inespecífico, indistinguible de otras miopatías inflamatorias. La biopsia muscular muestra la presencia de fibras necróticas, fibras en regeneración sin células inflamatorias significativas y una regulación positiva difusa o focal de la expresión del complejo mayor de histocompatibilidad de clase I. Los anticuerpos anti-3-hidroxi-3-metilglutaril-coenzima A (anti-HMG-CoA) reductasa representan un rasgo serológico característico de la SINAM. Caso clínico. Presentamos a un paciente que desarrolló debilidad muscular progresiva después de tomar simvastatina durante los últimos siete años. En la presentación inicial, su nivel de creatincinasa fue de 2.954 U/L y los anticuerpos anti-HMG-CoA reductasa fueron positivos. La biopsia mostró rasgos miopáticos profundos con numerosas fibras necróticas, algunas fibras en regeneración e infiltrado de células inflamatorias perimisial, combinado con una sobreexpresión difusa del complejo mayor de histocompatibilidad de clase I. Se le diagnosticó SINAM, se suspendió la estatina y se inició una dosis alta de corticoides sistémicos, inmunoglobulina intravenosa y metotrexato. Después de tres meses de seguimiento, tuvo una mejora significativa en la fuerza muscular y el nivel de creatincinasa volvió a la normalidad. Conclusiones. En este caso, la exclusión de miopatías inflamatorias, trastornos musculares metabólicos y otras enfermedades neurológicas es necesaria para establecer un diagnóstico fidedigno. En la SINAM, la simple suspensión de las estatinas a menudo es insuficiente, y es necesaria una terapia de inmunosupresión o inmunomodulación agresiva para lograr la remisión de la enfermedad. Este caso tiene como objetivo demostrar que las estatinas pueden inducir enfermedades musculares graves que requieren una inmunosupresión agresiva.

Dietary phytate induces subclinical mechanical allodynia in mice

Neuropathic pain is a condition with varying origins, including reduced dietary micronutrient intake. Phytate is a polyphosphate found in seeds and grains that can act as an antinutrient due to the ability of sequester essential divalent metals. Here we tested whether moderate dietary phytate intake could alter nociceptive pain. We subjected weaning mice to a chow supplemented with 1% phytate for eight weeks. Body weight gain, glycemic responses, food ingestion, water ingestion, and liver and adipose tissue weights were not altered compared to controls. We observed a decreased mechanical allodynia threshold in the intervention group, although there were no changes in heat- or cold-induced pain. Animals consuming phytate showed reduced spinal cord tumor necrosis factor (TNF), indicating altered inflammatory process. These data provide evidence for a subclinical induction of mechanical allodynia that is independent of phytate consumption in animals with otherwise normal phenotypic pattern.

Predictors of mortality in critically ill patients with COVID-19 and diabetes

The COVID-19 pandemic has challenged the entire world, and patients with diabetes mellitus (DM) have been particularly affected. We aimed to evaluate predictors of mortality during the first 30 days of hospitalization in critically ill patients with COVID-19 and comorbid DM. This prospective study included 110 critically ill patients admitted with COVID-19 infection. Thirty-two (29%) patients had a previous diagnosis of DM. Clinical variables, laboratory tests, and vascular biomarkers, such as VCAM-1, syndecan-1, ICAM-1, angiopoietin-1, and angiopoeitin-2, were evaluated after intensive care unit (ICU) admission. A comparison was made between patients with and without DM. No difference in mortality was observed between the groups (48.7 vs 46.9%, P=0.861). In the multivariate Cox regression analysis, VCAM-1 levels at ICU admission (HR: 1 [1-1.001], P<0.006) were associated with death in patients with DM. Among patients with DM, advanced age (HR 1.063 [1.031-1.096], P<0.001), increased Ang-2/Ang-1 ratio (HR: 4.515 [1.803-11.308] P=0.001), and need for dialysis (HR: 3.489 [1.409-8.642], P=0.007) were independent predictors of death. Higher levels of VCAM-1 in patients with DM was better at predicting death of patients with severe COVID-19 and comorbid DM, and their cut-off values were useful for stratifying patients with a worse prognosis. Vascular biomarkers VCAM-1 and Ang-2/Ang-1 ratio were predictors of death in patients with severe COVID-19 and comorbid DM and those without DM. Additionally, kidney injury was associated with an increased risk of death.

N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline, the major bioactive compound from Sideroxylon obtusifolium, attenuates pilocarpine-induced injury in cultured astrocytes.

Glial cells have been implicated in temporal lobe epilepsy in humans and in its models. Astrocytes are lost in several brain regions after acute seizures induced by pilocarpine and may suffer hyperplasia at subsequent time points. This study investigated the effect of N-methyl-(2S,4R)-trans-4-hydroxy-L-proline (NMP) on astrocytes exposed to cytotoxic concentrations of pilocarpine. Astrocytes were incubated with pilocarpine (half maximal inhibitory concentration (IC50)=31.86 mM) for 24 h. Afterwards, they were treated with NMP at concentrations ranging from 3.12 to 100 µg/mL for 24 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytoplasmic reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and rhodamine-123 (Rho123), respectively. Expression of glial fibrillary acidic protein (GFAP) and voltage-dependent anion channel-1 (VDAC-1) were measured by western blot. Pilocarpine significantly decreased cell viability and mitochondrial potential and increased ROS concentration significantly by 6.7 times compared to the control. NMP concentrations ≥25 µg/mL protected astrocytes against pilocarpine-induced injury in a concentration-dependent manner. Concomitantly, NMP reduced cytoplasmic ROS accumulation to 27.3, 24.8, and 12.3% in the groups treated with 25, 50, and 100 µg/mL NMP, respectively. NMP also protected mitochondria from pilocarpine-induced depolarization. These effects were associated with improvement of pilocarpine-induced GFAP and VDAC-1 overexpression, which are important biomarkers of astrocyte dysfunction. In conclusion, the improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes.

Using micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) for trace metal imaging in the development of MRI contrast agents for prostate cancer imaging.

BACKGROUND: Contrast agents (CA) are administered in magnetic resonance imaging (MRI) clinical exams to measure tissue perfusion, enhance image contrast between adjacent tissues, or provide additional biochemical information in molecular MRI. The efficacy of a CA is determined by the tissue distribution of the agent and its concentration in the extracellular space of all tissues. METHODS: In this work, micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) was used to examine and characterize a gadolinium-based zinc-sensitive agent (GdL2) currently under development for detection of prostate cancer (PCa) by MRI. Prostate tissue samples were collected from control mice and mice with known PCa after an MRI exam that included injection of GdL2. The samples were raster scanned to investigate trends in Zn, Gd, Cu, Fe, S, P, and Ca. RESULTS: Significant Zn and Gd co-localization was observed in both healthy and malignant tissues. In addition, a marked decrease in Zn was found in the lateral lobe of the prostate obtained from mice with PCa. CONCLUSION: We demonstrate here that µ-SRXRF is a useful tool for monitoring the distribution of several elements including Zn and Gd in animal models of cancer. The optimized procedures for tissue preparation, processing, data collection, and analysis are described.

Burden of phenylketonuria in Latin American patients: a systematic review and meta-analysis of observational studies.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase. If untreated, the complications of PKU lead to significant neucognitive and neuropsychiatric impairments, placing a burden on both the individual's quality of life and on the healthcare system. We conducted a systematic literature review to characterize the impact of PKU on affected individuals and on healthcare resources in Latin American (LATAM) countries. METHODS: Searches of the global medical literature as well as regional and local medical literature up to September 2021. Observational studies on patients with PKU from any LATAM country. Pairs of reviewers independently screened eligible articles, extracted data from included studies, and assessed their risk of bias. RESULTS: 79 unique studies (47 cross-sectional studies, 18 case series, 12 case reports, and two cohort studies) with a total of 4090 patients were eligible. Of these studies, 20 had data available evaluating early-diagnosed PKU patients for meta-analysis of burden outcomes. Intellectual disability in the pooled studies was 18% [95% Confidence Interval (CI) 0.04-0.38; I2 = 83.7%, p = 0.0133; two studies; n = 114]. Motor delay was 15% [95% CI 0.04-0.30; I2 = 74.5%, p = 0.0083; four studies; n = 132]. Speech deficit was 35% [95% CI 0.08-0.68; I2 = 93.9%, p < 0.0001; five studies; n = 162]. CONCLUSIONS: There is currently evidence of high clinical burden in PKU patients in LATAM countries. Recognition that there are many unmet neuropsychological needs and socioeconomic challenges faced in the LATAM countries is the first step in planning cost-effective interventions.

Does Chlorination Promote Antimicrobial Resistance in Waterborne Pathogens? Mechanistic Insight into Co-Resistance and Its Implication for Public Health.

Chemical agents including chlorine and antibiotics are used extensively to control infectious microorganisms. While antibiotics are mainly used to treat bacterial infections, chlorine is widely used for microbial inactivation in the post-secondary disinfection steps of water treatment. The extensive use of these agents has been acknowledged as a driving force for the expansion of antimicrobial resistance (AMR) and has prompted discourse on their roles in the evolution and proliferation of resistant pathogens in the aquatic milieus. We live in a possible "post-antibiotic" era when resistant microbes spread at startling levels with dire predictions relating to a potential lack of effective therapeutic antibacterial drugs. There have been reports of enhancement of resistance among some waterborne pathogens due to chlorination. In this context, it is pertinent to investigate the various factors and mechanisms underlying the emergence and spread of resistance and the possible association between chlorination and AMR. We, therefore, reflect on the specifics of bacterial resistance development, the mechanisms of intrinsic and acquired resistance with emphasis on their environmental and public health implications, the co-selection for antibiotic resistance due to chlorination, biofilm microbiology, and multidrug efflux activity. In-depth knowledge of the molecular basis of resistance development in bacteria will significantly contribute to the more rational utilization of these biocidal agents and aid in filling identified knowledge gap toward curbing resistance expansion.