Hematopoietic Stem Cell Transplantation in Children with Sickle Cell Disease and Thalassemia Major: A National Database Study.

In patients with sickle cell disease (SCD) and beta-thalassemia major (TM), allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment option with a good survival rate. However, with the recent approval of gene therapies, more information is needed to understand the benefits and risks of these interventions. We performed a retrospective analysis of the Kids Inpatient Database to describe demographic features, short-term complications, and hospital charges of patients with SCD and TM treated with HSCT during 2006-2019 in the United States. The database was filtered using the International Classification of Diseases, 9th and 10th edition codes to identify children under 20 years of age with SCD or TM who underwent HSCT. A total of 513 children with SCD or TM who received HSCT were analyzed. The prevalence of HSCT per 1000,000 U.S. population increased from 0.31 in 2006 to 1.99 in 2019 (p < 0.001). The median age of children with SCD who underwent HSCT was 10 (6-15) years, and that for TM was 6 (3-11.5) years (p < 0.001). The combined mortality rate was 4% (2.4%-6.6%) but higher in the TM group. The length-of-stay and total charges were higher in the TM population (p < 0.01). This study provides national data on HSCT among hospitalized children with SCD and TM in the United States, demonstrating an increasing use of HSCT between 2006 and 2019. Although hospital mortality of HSCT in these conditions is low, it still represents a challenge, especially in TM patients.

Computational 3D Models of Fe2+/3+-Aß1-42 Complexes Associated with Alzheimer's Disease.

The interaction between iron and amyloid-beta (Aß) peptides has received significant attention in Alzheimer's disease (AD) research due to its potential implications in developing this pathology. However, the coordination preferences of iron and Aß1-42 have not been thoroughly investigated or remain unknown. This study employs a computational protocol that combines homology modeling techniques with quantum mechanics (DTF-xTB) calculations to build and evaluate several 3D models of Fe2+/3+-Aß1-42. Our results reveal well-defined complexes for both the metal and peptide moieties, and we discuss the molecular interactions stabilizing these complexes by elucidating the coordinating environments and binding preferences. These proposed models offer valuable insights into the role of iron in Alzheimer's disease (AD) pathology.

Preparation and Characterization of Zinc Ferrite and Gadolinium Iron Garnet Composite for Biomagnetic Applications.

Cancer is a major worldwide public health problem. Although there have already been astonishing advances in cancer diagnosis and treatment, the scientific community continues to make huge efforts to develop new methods to treat cancer. The main objective of this work is to prepare, using a green sol-gel method with coconut water powder (CWP), a new nanocomposite with a mixture of Gd3Fe5O12 and ZnFe2O4, which has never been synthesized previously. Therefore, we carried out a structural (DTA-TG and X-ray diffraction), morphological (SEM), and magnetic (VSM and hyperthermia) characterization of the prepared samples. The prepared nanocomposite denoted a saturation magnetization of 11.56 emu/g at room temperature with a ferromagnetic behavior and with a specific absorption rate (SAR) value of 0.5 ± 0.2 (W/g). Regarding cytotoxicity, for concentrations < 10 mg/mL, it does not appear to be toxic. Although the obtained results were interesting, the high particle size was identified as a problem for the use of this nanocomposite.

RISK FACTORS AT NON-UNION OF TIBIAL FRACTURE TREATED WITH INTRAMEDULLARY NAIL.

Objective: Identify the predictors associated with delayed union at 6 months and non-union at 12 months in tibial shaft fractures treated with intramedullary nailing (IMN). Methods: This retrospective longitudinal study included a cohort of 218 patients who sustained tibial shaft fractures and received IMN between January 2015 and March 2022. We gathered data on a range of risk factors, including patient demographics, trauma intensity, associated injuries, fracture characteristics, soft tissue injuries, comorbidities, addictions, and treatment-specific factors. We employed logistic bivariate regression analysis to explore the factors predictive of delayed union and non-union. Results: At the 6-month follow-up, the incidence of delayed union was 28.9%. Predictors for delayed union included flap coverage, high-energy trauma, open fractures, the use of external fixation as a staged treatment, the percentage of cortical contact in simple type fractures, RUST score, and postoperative infection. After 12 months, the non-union rate was 15.6%. Conclusion: the main predictors for non-union after IMN of tibial shaft fractures are related to the trauma energy. Furthermore, the initial treatment involving external fixation and postoperative infection also correlated with non-union. Level of Evidence III; Retrospective Longitudinal Study.

Objetivo: identificar os fatores preditivos associados ao atraso de consolidação em 6 meses e à não união em 12 meses em fraturas da diáfise da tíbia tratadas com haste intramedular (HIM). Métodos: O estudo longitudinal retrospectivo de coorte incluiu 218 pacientes, que apresentaram fraturas da díafise da tíbia e receberam HIM entre janeiro de 2015 e março de 2022. Os desfechos principais pesquisados foram atraso de consolidação em 6 meses de acompanhamento, e não união em 12 meses. Coletou-se dados de uma variedade de fatores de risco. Utilizou-se análise de regressão logística bivariada para explorar os fatores preditivos de atraso de consolidação e não união. Resultados: Aos 6 meses, a incidência de atraso de consolidação foi de 28,9%. Os preditores de atraso de consolidação incluem cobertura de retalho, trauma de alta energia, fraturas expostas, uso de fixação externa como tratamento estagiado, porcentagem de contato cortical em fraturas simples, escore RUST e infecção pós-operatória. Após 12 meses, a taxa de não união foi de 15,6%, com fatores preditivos sendo necessidade de cobertura por retalho, lesão vascular, trauma de alta energia, fraturas expostas, uso de fixação externa como tratamento estagiado, porcentagem de contato cortical em fraturas simples e infecção pós-operatória. Nível de Evidência III; Estudo Longitudinal Retrospectivo.

LOW INFECTION AND NON-UNION RATES IN POLYTRAUMA FEMORAL FRACTURES: A RETROSPECTIVE STUDY.

Objective: Assess complications and risks in staged femoral shaft fracture treatment using external fixation and intramedullary nailing (DCO). Methods: Analysis involved 37 patients with 40 fractures, mostly male (87.5%), average age 32.9 years. Data included ASA score, AO/OTA and Gustilo classifications, Glasgow Coma Score, Injury Severity Score, times to external fixation and conversion, ICU duration, nail type, and reaming status. Complications tracked were mortality, deep infection, and non-union. Results: Predominant fracture type was AO/OTA A (45%), with 40% open (Gustilo A, 93.8%). Average ISS was 21; GCS was 12.7. Median ICU stay was 3 days; average time to conversion was 10.2 days. Retrograde nails were used in 50% of cases, with reaming in 67.5%. Complications included deep infections in 5% and non-union in 2.5%. Conclusion: DCO strategy resulted in low infection and non-union rates, associated with lower GCS and longer ICU stays. Level of Evidence III; Retrospective Cohort Study.

Objetivo: Analisar taxa de complicações e riscos no tratamento estagiado de fraturas diafisárias do fêmur com fixador externo e conversão para haste intramedular (DCO). Métodos: Estudo com 37 pacientes, 35 masculinos, idade média de 32,9 anos, abordando escores ASA, classificação AO/OTA, Gustilo, Glasgow e ISS, tempo até a fixação externa, na UTI e tipo de haste. Complicações como mortalidade, infecção profunda e não união foram registradas. Resultados: Fraturas tipo AO/OTA A foram as mais comuns (45%), com 40% expostas (Gustilo A, 93,8%). ISS médio de 21 e ECG de 12,7. Média de 3 dias na UTI e 10,2 dias até a conversão. Uso de haste retrógrada em 50% dos casos e fresagem em 67,5%. As complicações incluíram infecção profunda em 5% e não união em 2,5%. A não união correlacionou-se com baixo ECG e tempo prolongado na UTI. Conclusão: A estratégia de DCO mostrou-se eficaz com baixas taxas de infecção e não união, associada a baixo ECG e tempo na UTI. Nível de Evidência III; Estudo de Coorte Retrospectivo.

Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and risk factors associated with high total bacterial count in bulk tank milk from dairy farms in Colombia.

The objective of the study was to evaluate the frequency and genetic characteristics of ESBL-producing Escherichia coli and Klebsiella spp. and the risk factors associated with a high total bacterial count in bulk tank milk samples of dairy farms in three municipalities of the Antioquia Department, Colombia. Fifteen samples were positive for E. coli and Klebsiella spp. Subsequent analysis of the 16 S rRNA gene sequences confirmed these isolates included E. coli (n = 3), K. oxytoca (n = 11), and K. pneumoniae (n = 1). None of the isolates was positive for ESBL identification by phenotypic methods, but the only the isolate of K. pneumoniae was positive for the blaSHV61 gene by sequence analysis. The antibiotic susceptibility evaluation for all Klebsiella spp. isolates identified resistance to fosfomycin (50%; 6/12) and ampicillin (100%; 12/12). While most of the herds maintain adequate hygienic quality, specific risk factors such as having more than 60 milking cows, frequent changes in milkers, milking in paddocks, and using a chlorinated product for pre-dipping have been identified as associated with a high total bacterial count > 100,000 CFU/mL in bulk tank milk. However, certain variables including the milker being the owner of the animals and the proper washing and disinfection of the milking machine contribute to maintain a high level of hygiene and quality in the raw milk stored in the tanks. In conclusion, the frequency of ESBL producers was relatively low, with only K. pneumoniae testing positive for the blaSHV ESBL type. The presence of these bacteria in milk tanks represents a potential risk to public health for consumers of raw milk and its derivatives.

Autochtonal case of chronic, unifocal, pulmonary paracoccidioidomycosis with methotrexate use, in Salvador ‒ Brazil.

We report an autochthonous case of mild unifocal chronic pulmonary paracoccidioidomycosis in a 48-year-old previously healthy woman with no history of possible environmental exposures in endemic rural areas, supposedly resulting from reactivation of a latent pulmonary focus secondary to the use of methotrexate for the control of Chikungunya arthropathy. Laboratory investigation ruled out other immunosuppression. Her only symptoms were a dry cough and chest pain. Diagnosis confirmed by needle lung biopsy. There were no abnormalities on physical examination nor evidence of central nervous system involvement. MRI of the total abdomen showed no involvement of other organs. Computed chest tomography showed a favorable evolution under the use of itraconazole (200 mg/day). Different tomographic presentations findings are highlighted when performed before and after treatment. CONCLUSIONS: PCM should be considered even in a woman without a history of consistent environmental exposure and in a non-endemic geographic area.

Cryoprotective Polysaccharides with Ordered Gel Structures Induce Ice Growth Anticipation and Survival Enhancement during Cell Cryopreservation.

This work cross-correlated rheological, thermodynamic, and conformational features of several natural polysaccharides to their cryoprotective performance. The basis of cryoprotection of FucoPol, pectin, and agar revealed a causal combination of (i) an emerging sol-gel transition (p = 0.014) at near-hypothermia (4 °C), (ii) noncolligative attenuated supercooling of the kinetic freezing point of water (p = 0.026) supporting ice growth anticipation, and (iii) increased conformational order (p < 0.0001), where helix-/sheet-like features boost cryoprotection. FucoPol, of highest cryoprotective performance, revealed a predominantly helical structure (α/ß = 1.5) capable of forming a gel state at 4 °C and the highest degree of supercooling attenuation (TH = 6.2 °C). Ice growth anticipation with gel-like polysaccharides suggests that the gel matrix neutralizes elastic deformations and lethal cell volumetric fluctuations during freezing, thus preventing the loss of homeostasis and increasing post-thaw viability. Ultimately, structured gels capable of attenuated supercooling enable cryoprotective action at the polymer-cell interface, in addition to polymer-ice interactions. This rationale potentiates implementing alternative, biobased, noncytotoxic polymers in cryobiology.

A Thermoresponsive injectable drug delivery system of chitosan/ß-glycerophosphate with gellan gum/alginate microparticles.

The development of new Drug Delivery Systems (DDS) by incorporating microparticles within hydrogels can prolong the release rate of drugs and/or other bioactive agents. In this study, we combined gellan gum/alginate microparticles within a thermoresponsive chitosan (Ch) hydrogel with ß-Glycerophosphate (ß-GP), designing the system to be in the sol state at 21 °C and in the gel state at 37 °C to enable the injectability of the system. The system was in the sol state between 10 °C and 21 °C. Higher concentrations of ß-GP (0, 2, 3, 4, 5 w/v%) and microparticles (0, 2 and 5 w/v%) allowed a faster sol-gel transition with higher mechanical strength at 37 °C. However, the sol-gel transition was not instantaneous. The release profile of methylene blue (MB) from the microparticles was significantly affected by their incorporation in Ch/ß-GP hydrogels, only allowing the release of 60-70 % of MB for 6 days, while the microparticles alone released all the MB in 48 h. The proposed system did not present cytotoxicity to VERO cell lines as a preliminary assay, with the Ch/ß-GP/GG:Alg having >90 % of cellular viability. The proposed Ch/ß-GP system proved to have a delaying effect on drug release and biocompatible properties, being a promising future DDS.

Pyrazoles have a multifaceted anti-inflammatory effect targeting prostaglandin E2, cyclooxygenases and leukocytes' oxidative burst.

Elevated levels of prostaglandin E2 have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of cyclooxygenase enzymatic activity, thereby leading to the suppression of prostaglandin E2, are often associated with several side effects due to their non-specific inhibition of cyclooxygenase enzymes. Consequently, the targeted suppression of prostaglandin E2 production with innovative molecules and/or mechanisms emerges as a compelling therapeutic strategy for the treatment of inflammatory-related diseases. Therefore, in this study, a systematic analysis of 28 pyrazole derivatives was conducted to explore their potential mechanisms for reducing prostaglandin E2 levels. In this context, the evaluation of these derivatives extended to examining their capacity to reduce prostaglandin E2in vitro in human whole blood, inhibit cyclooxygenase-1 and cyclooxygenase-2 enzymes, modulate cyclooxygenase-2 expression, and suppress oxidative burst in human leukocytes. The results enabled the establishment of significant structure-activity relationships, elucidating key determinants for their activities. In particular, the 4-styryl group on the pyrazole moiety and the presence of chloro substitutions were identified as key determinants. Pyrazole 8 demonstrated the capacity to reduce prostaglandin E2 levels by downregulating cyclooxygenase-2 expression, and pyrazole-1,2,3-triazole 18 emerged as a dual-acting agent, inhibiting human leukocytes' oxidative burst and cyclooxygenase-2 activity. Furthermore, pyrazole 26 demonstrated effective reduction of prostaglandin E2 levels through selective cyclooxygenase-1 inhibition. These results underscore the multifaceted anti-inflammatory potential of pyrazoles, providing new insights into the substitutions and structural frameworks that are beneficial for the studied activity.

Exploring the Impact of Copper Oxide Substitution on Structure, Morphology, Bioactivity, and Electrical Properties of 45S5 Bioglass®.

In recent decades, the requirements for implantable medical devices have increased, but the risks of implant rejection still exist. These issues are primarily associated with poor osseointegration, leading to biofilm formation on the implant surface. This study focuses on addressing these issues by developing a biomaterial for implant coatings. 45S5 bioglass® has been widely used in tissue engineering due to its ability to form a hydroxyapatite layer, ensuring a strong bond between the hard tissue and the bioglass. In this context, 45S5 bioglasses®, modified by the incorporation of different amounts of copper oxide, from 0 to 8 mol%, were synthesized by the melt-quenching technique. The incorporation of Cu ions did not show a significant change in the glass structure. Since the bioglass exhibited the capacity for being polarized, thereby promoting the osseointegration effectiveness, the electrical properties of the prepared samples were studied using the impedance spectroscopy method, in the frequency range of 102-106 Hz and temperature range of 200-400 K. The effects of CuO on charge transport mobility were investigated. Additionally, the bioactivity of the modified bioglasses was evaluated through immersion tests in simulated body fluid. The results revealed the initiation of a Ca-P-rich layer formation on the surface within 24 h, indicating the potential of the bioglasses to enhance the bone regeneration process.

GNB1 and obesity: Evidence for a correlation between haploinsufficiency and syndromic obesity.

Most patients with GNB1 encephalopathy have developmental delay and/or intellectual disability, brain anomalies and seizures. Recently, two cases with GNB1 encephalopathy caused by haploinsufficiency have been reported that also show a Prader-Willi-like phenotype of childhood hypotonia and severe obesity. Here we present three new cases from our expert centre for genetic obesity in which GNB1 truncating and splice variants, probably leading to haploinsufficiency, were identified. They all have obesity, hyperphagia and intellectual deficit. The clinical cases and their weight courses are presented, together with a review of all 68 published cases with GNB1 encephalopathy. Information on weight was not mentioned in most of these articles, so we contacted authors for additional clinical information on weight status and hyperphagia. Of the 42 patients whose weight status we could determine, obesity was present in 8 patients (19%). Obesity is significantly over-represented in the group with truncating and splicing variants. In this group, we see an obesity prevalence of 75%. Since GNB1 has been linked to several key genes in the hypothalamic leptin-melanocortin pathway, which regulates satiety and energy expenditure, our data support the potential association between GNB1 haploinsufficiency and genetic obesity. We also suggest GNB1 is a candidate gene for the known obesity phenotype of the 1p36 microdeletion syndrome given this chromosomal region includes the GNB1 gene. Knowledge of an additional obesity phenotype is important for prognosis, early interventions against obesity and awareness when prescribing weight-inducing medication.

Bioactive Hydroxyapatite Aerogels with Piezoelectric Particles.

Open-cell foams based on hydroxyapatite (HAp) can mimic the extracellular matrix (ECM) to better replace damaged hard tissues and assist in their regeneration processes. Aerogels of HAp nanowires (NW) with barium titanate (BT) particles were produced and characterized regarding their physical and chemical properties, bioactivity, and in vitro cytotoxicity. Considering the role of piezoelectricity (mainly due to collagen) and surface charges in bone remodeling, all BT particles, of size 280 nm and 2 and 3 µm, contained BaTiO3 in their piezoelectric tetragonal phase. The synthesized nanowires were verified to be AB-type carbonated hydroxyapatite. The aerogels showed high porosity and relatively homogeneous distribution of the BT particles. Barium titanate proved to be non-cytotoxic while all the aerogels produced were cytotoxic for an extract concentration of 1 mg/mL but became non-cytotoxic at concentrations of 0.5 mg/mL and below. It is possible that these results were affected by the higher surface area and quicker dissolution rate of the aerogels. In the bioactivity assays, SEM/EDS, it was not easy to differentiate between the apatite deposition and the surface of the HAp wires. However, a quantitative EDS analysis shows a possible CaP deposition/dissolution cycle taking place.

Multi-datasets to monitor and assess meteorological and hydrological droughts in a typical basin of the Brazilian semiarid region.

This study analyzed the meteorological and hydrological droughts in a typical basin of the Brazilian semiarid region from 1994 to 2016. In recent decades, this region has faced prolonged and severe droughts, leading to marked reductions in agricultural productivity and significant challenges to food security and water availability. The datasets employed included a digital elevation model, land use and cover data, soil characteristics, climatic data (temperature, wind speed, solar radiation, humidity, and precipitation), runoff data, images from the MODIS/TERRA and AQUA sensors (MOD09A1 and MODY09A1 products), and soil water content. A variety of methods and products were used to study these droughts: the meteorological drought was analyzed using the Standardized Precipitation Index (SPI) derived from observed precipitation data, while the hydrological drought was assessed using the Standardized Soil Index (SSI), the Nonparametric Multivariate Standardized Drought Index (NMSDI), and the Parametric Multivariate Standardized Drought Index (PMSDI). These indices were determined using water balance components, including streamflow and soil water content, from the Soil Water Assessment Tool (SWAT) model, and evapotranspiration data from the Surface Energy Balance Algorithm for Land (SEBAL). The findings indicate that the methodology effectively identified variations in water dynamics and drought periods in a headwater basin within Brazil's semiarid region, suggesting potential applicability in other semiarid areas. This study provides essential insights for water resource management and resilience building in the face of adverse climatic events, offering a valuable guide for decision-making processes.

Stress Inoculation in Police Officers Using Virtual Reality: A Controlled Study.

Policing is a highly demanding and stressful profession. Virtual reality (VR) has emerged as a promising tool for enhancing stress management programs, including for police officers. The use of VR in combination with biosensors enables measurement of psychophysiological responses such as peripheral temperature (PT) and skin conductance level (SCL). This study investigated the psychophysiological responses of police officers exposed to a VR scenario simulating a car accident. The study included a total of 63 police officers from the Public Security Police. Participants were divided into three groups based on their police divisions: the Investigation Brigade of Traffic Accidents, the Traffic Surveillance Squad (TSS), and a control group from the Lisbon Metropolitan Command. The results indicated that the VR environment effectively induced psychophysiological arousal, particularly in less experienced officers (TSS), that is, there were significant group differences in mean SCL and PT, showing this group with higher SCL and lower PT during the VR exposure. These results support the potential of VR as a stress inoculation strategy for training police officers and highlight the complex nature of stress responses that are influenced by individual factors and psychopathology.

Plant Monoterpenes and Essential Oils as Potential Anti-Ageing Agents: Insights from Preclinical Data.

Ageing is a natural process characterized by a time-dependent decline of physiological integrity that compromises functionality and inevitably leads to death. This decline is also quite relevant in major human pathologies, being a primary risk factor in neurodegenerative diseases, metabolic disorders, cardiovascular diseases and musculoskeletal disorders. Bearing this in mind, it is not surprising that research aiming at improving human health during this process has burst in the last decades. Importantly, major hallmarks of the ageing process and phenotype have been identified, this knowledge being quite relevant for future studies towards the identification of putative pharmaceutical targets, enabling the development of preventive/therapeutic strategies to improve health and longevity. In this context, aromatic plants have emerged as a source of potential bioactive volatile molecules, mainly monoterpenes, with many studies referring to their anti-ageing potential. Nevertheless, an integrated review on the current knowledge is lacking, with several research approaches studying isolated ageing hallmarks or referring to an overall anti-ageing effect, without depicting possible mechanisms of action. Herein, we aim to provide an updated systematization of the bioactive potential of volatile monoterpenes on recently proposed ageing hallmarks, and highlight the main mechanisms of action already identified, as well as possible chemical entity-activity relations. By gathering and categorizing the available scattered information, we also aim to identify important research gaps that could help pave the way for future research in the field.

Electrospun Polycaprolactone Membranes Expanded with Chitosan Granules for Cell Infiltration.

The small pore size of electrospun membranes prevents their use as three-dimensional scaffolds. In this work, we produced polycaprolactone (PCL) electrospun fibrous membranes with expanded pores by incorporating chitosan (CS) granules into the PCL solution. Scanning electron microscopy images confirmed the presence of the CS granules embedded in the PCL fibers, creating an open structure. Tensile testing results showed that the addition of CS decreased both Young's modulus and the yield stress, but co-electrospun membranes (PCL fibers blended with CS-containing PCL fibers) exhibited higher values compared to single electrospun membranes (CS-containing PCL fibers). Human fibroblasts adhered to and proliferated on all scaffolds. Nuclear staining revealed that cells populated the entire scaffold when CS granules were present, while in PCL membranes, cells were mostly limited to the surface due to the small pore size. Overall, our findings demonstrate that electrospun membranes containing CS granules have sufficiently large pores to facilitate fibroblast infiltration without compromising the mechanical stability of the structure.

Resistant anemia in a kidney transplant recipient: Pure red cell aplasia due to parvovirus B19 infection.

Anemia in kidney transplant recipients can stem from a diverse array of etiologies, including dietary deficiencies, inflammatory processes, allograft dysfunction, as well as viral and bacterial infections. We present a case of refractory anemia in a 49-year-old male patient occurring within the initial month following a kidney transplant, which persisted despite numerous transfusions, posing a formidable challenge. The patient was maintained on the standard immunosuppressant regimen-Tacrolimus, Mycophenolate, and Prednisolone. Diagnostic evaluations eliminated well-established causes such as dietary deficiencies, gastrointestinal losses, and prevalent infections. Subsequently, after viral PCR testing, a diagnosis of Pure Red Cell Aplasia (PRCA) due to infection with parvovirus B19 was made. Although the patient had a reduction in the immunosuppression drugs and received a course of Intravenous Immunoglobulins (IVIG) on two separate occasions spanning two months, the anemia relapsed. Subsequently, after an additional dose of IVIG with further modification and reduction of the immunosuppressant regimen, including stopping the mycophenolate and switching tacrolimus with cyclosporine, the patient ultimately achieved successful resolution of his symptoms and a significant decrease in viral load. Our case highlights the significance of unconventional etiologies when confronted with anemia in the setting of kidney transplantation. Furthermore, it also provides further insights into therapeutic avenues for addressing PRCA in kidney transplant recipients.