Priorities, opportunities, and challenges for integrating microorganisms into Earth system models for climate change prediction.

Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a "top 10" list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy.

Preoperative computed tomography, surgical treatment and long-term outcomes of dogs with abscesses on migrating vegetal foreign bodies and oropharyngeal stick injuries: 39 cases (2010-2021).

OBJECTIVES: This study evaluated success rates of surgical treatment of head and neck abscesses and draining tracts for suspected migrating vegetal foreign body and oropharyngeal penetrating injuries, and compared the outcomes according to whether a vegetal foreign body was identified in preoperative computed tomography (CT) examination. MATERIALS AND METHODS: This retrospective study involved 39 dogs that underwent CT and subsequent surgical exploration of abscesses and/or draining tracts in the head and neck, in a single institution between 2010 and 2021. Recorded data included signalment, history, physical examination, CT and surgical findings. The postoperative follow-up period was at least 8 months. Cases were classified according to whether a foreign body was identified on CT or was only suspected because of the presence of cavities and/or draining tracts on CT. RESULTS: A vegetal foreign body was identified on CT in 11 of 39 cases and later confirmed at surgery in 10 cases. In 28 of 39 cases, a vegetal foreign body was not identified on CT, but in seven of these 28 cases it was found at surgery. Resolution of clinical signs was achieved in 11 of 11 cases when a vegetal foreign body was identified on CT and in 26 of 28 cases without a foreign body identified on CT. Two cases of recurrence were observed in animals in which no foreign body was detected. CLINICAL SIGNIFICANCE: In this population of dogs undergoing surgery after preoperative CT scan, we observed resolution of clinical signs after a single surgical procedure in 95% of the cases. All animals in which a foreign body was identified were cured.

Different agricultural practices affect soil carbon, nitrogen and phosphorous in Kilombero -Tanzania.

Converting natural and semi-natural vegetation to agriculture is currently the most significant land use change at global scale. This conversion leads to changes in soil nutrients and increased CO2 emissions. However, knowledge of how soil organic carbon and nutrients change under various farming management is still limited, especially for small scale farming systems. This study evaluated the effects of different farming systems on soil organic carbon (SOC), total nitrogen (TN) and total phosphorous (TP) in subsistence farming at Kilombero, Tanzania. We applied an in-situ experimental setup, comparing maize and rice farming with and without irrigation and difference in fertilizers, with replicated soil sampling at five soil depths to a depth of 60 cm. The results show that irrigation had a positive effect on profile-averaged concentrations of SOC and TN, while fertilization had a positive effect on TN. Higher concentrations and stocks of TN were found in maize field soils compered to rice fields. In the vertical profile, irrigation and fertilization had positive effects on concentrations of SOC and TN of top soil layers, and the interaction between irrigation and fertilization extended the effect to deeper soil layers. Our results indicate that moderate irrigation and fertilization can help to improve carbon storage and nutrient availability (TN) in small-scale farming soils in Africa.

Amendment of the OMERACT ultrasound definitions of joints' features in healthy children when using the DOPPLER technique.

BACKGROUND: Recently preliminary ultrasonography (US) definitions, in B mode, for normal components of pediatric joints have been developed by the OMERACT US group. The aim of the current study was to include Doppler findings in the evaluation and definition of normal joint features that can be visualized in healthy children at different age groups. METHODS: A multistep approach was used. Firstly, new additional definitions of joint components were proposed during an expert meeting. In the second step, these definitions, along with the preliminary B-mode-US definitions, were tested for feasibility in an exercise in healthy children at different age groups. In the last step, a larger panel of US experts were invited to join a web-based consensus process in order to approve the developed definitions using the Delphi methodology. A Likert scale of 1-5 was used to assess agreement. RESULTS: Physiological vascularity and fat pad tissue were identified and tested as two additional joint components in healthy children. Since physiological vascularity changes over the time in the growing skeleton, the final definition of Doppler findings comprised separate statements instead of a single full definition. A total of seven statements was developed and included in a written Delphi questionnaire to define and validate the new components. The final definitions for fat pad and physiological vascularity agreed by the group of experts reached 92.9% and 100% agreement respectively in a web survey. CONCLUSION: The inclusion of these two additional joints components which are linked to detection of Doppler signal in pediatric healthy joints will improve the identification of abnormalities in children with joint pathologies.

Impact of involvement of individual joint groups on subdimensions of functional ability scales in juvenile idiopathic arthritis.

OBJECTIVE: To investigate the influence of arthritis in individual joint groups on subdimensions of functional ability questionnaires in children with juvenile idiopathic arthritis (JIA). METHODS: 206 patients were included who had the Childhood Health Assessment Questionnaire (C-HAQ) and the Juvenile Arthritis Functionality Scale (JAFS) completed simultaneously by a parent and received a detailed joint assessment. In each patient, joint involvement (defined as presence of swelling, pain on motion/tenderness and/or restricted motion) was classified in 3 topographic patterns: Pattern 1 (hip, knee, ankle, subtalar and foot joints); Pattern 2 (wrist and hand joints); Pattern 3 (elbow, shoulder, cervical spine and temporomandibular joints). Frequency of reported disability in each instrument subdimension was evaluated for each joint pattern, present either isolatedly or in mixed form. RESULTS: Among patients with Pattern 1, the JAFS revealed the greatest ability to capture and discriminate functional limitation, whereas impairment in the C-HAQ was more diluted across several subdimensions. Both C-HAQ and JAFS appeared to be less reliable in detecting functional impairment in the hand and wrist (Pattern 2) than in other body areas. Overall, the JAFS revealed a superior ability to discriminate the relative functional impact of impairment in individual joint groups among patients with mixed joint patterns. CONCLUSION: In children with JIA, a functional measure focused to assess the function of individual joint groups (the JAFS) may detect with greater precision the functional impact of arthritis in specific body areas than does a standard questionnaire based on the assessment of activities of daily living (the C-HAQ).

Point mutations and a large intragenic deletion in SPG11 in complicated spastic paraplegia without thin corpus callosum.

BACKGROUND: Hereditary spastic paraplegia (HSP) with thin corpus callosum (HSP-TCC) is a frequent subtype of complicated HSP clinically characterised by slowly progressive spastic paraparesis with cognitive impairment and thin corpus callosum (TCC). SPG11, the gene associated with the major locus involved, encodes spatacsin, a protein of unknown function. METHODS: Different types of mutations were identified in patients with the complex form of HSP (cHSP) including TCC. We screened a series of 45 index patients with different types of cHSP with (n = 10) and without (n = 35) TCC. RESULTS: Ten mutations, of which five are novel, were detected in seven patients. Of importance, three out of seven mutated patients present with cHSP without TCC. Among the novel mutations identified, we characterised a large intragenic rearrangement deleting 2.6 kb of the SPG11 gene. The rearrangement is due to non-allelic homologous recombination between Alu sequences flanking the breakpoints. CONCLUSIONS: These findings expand the mutation spectrum of SPG11 and suggest that SPG11 mutations may occur more frequently in familial than sporadic forms of cHSP without TCC. This helps to define further clinical and molecular criteria for a correct diagnosis of the SPG11 related form of cHSP. In addition, the intragenic deletion detected here, and the mechanism involved, both provide clues to address the issue of SPG11 missing mutant alleles previously reported.

Factors affecting survival in juvenile systemic sclerosis.

OBJECTIVES: To determine whether demographic, clinical and immunological features may predict the outcome in juvenile SSc (JSSc). METHODS: Clinical and laboratory characteristics of patients with JSSc collected from paediatric rheumatology centres worldwide were analysed. First, univariate tests identified those features significantly related with fatal outcome, and then multivariate logistic regression analysis was applied to determine the predictors of mortality. RESULTS: One hundred and thirty-four patients from 40 centres were eligible for the analysis. Sixteen patients died and a rapidly fatal course was observed in most of them: 4/16 died within 1 yr after diagnosis and 10/16 within 5 yrs. At the moment of diagnosis, patients with poor outcome showed a significantly higher frequency of internal organ involvement, particularly cardiac, respiratory and gastrointestinal systems. No significant difference emerged for entity of skin, vascular and musculo-skeletal involvement, nor for auto-antibodies profile and laboratory tests. Multivariate analysis showed the following factors to be significant predictors of mortality: fibrosis on chest X-rays [odds ratio (OR) 11.2], raised creatinine levels (OR 22.7) and pericarditis (OR 41.3), while a short disease duration at diagnosis conferred protection (OR 0.3). CONCLUSIONS: All patients with JSSc and fatal outcome were affected by the diffuse form of the disease, and most of them showed a very rapid progression and early signs of internal organ involvement. This suggests that, in children, SSc may have two possible courses: a rapid development of internal organ failure leading to severe disability and eventually to death, or a slow course of the disease with lower mortality.

Preliminary evidence that etanercept may reduce radiographic progression in juvenile idiopathic arthritis.

OBJECTIVE: To investigate the rate of radiographic progression, as measured with the carpo-metacarpal ratio (Poznanski score), during etanercept (ETN) therapy in children with polyarticular juvenile idiopathic arthritis (JIA). METHODS: Patients included in the Italian ETN registry who had a standard radiograph of both hands and wrists in the posteroanterior view made at start of treatment and after 1 year were included in the study. The clinical response was assessed by means of the ACR Pediatric definition of improvement. Radiographic progression was determined by calculating the change in the Poznanski score between the baseline and the 1-year radiographs. RESULTS: A total of 40 patients were studied. The frequency of ACR pediatric 30, 50, and 70 response at 1 year was 77%, 72%, and 50%, respectively. The median change in the Poznanski score between baseline and 1 year was + 0.3 units, meaning that, on average, patients experienced improvement in radiographic progression. CONCLUSION: Our pilot study provides evidence that ETN is potentially capable of reducing the progression of radiographic joint damage in JIA. This finding deserves confirmation in a controlled trial.

The magnitude of early response to methotrexate therapy predicts long-term outcome of patients with juvenile idiopathic arthritis.

OBJECTIVE: To investigate the relationship between the magnitude of clinical response in the first 6 months of methotrexate (MTX) therapy and long-term outcome in children with juvenile idiopathic arthritis (JIA). METHODS: The clinical charts of 125 JIA patients who were started with MTX and then followed for at least 5 years were reviewed. Based on the level of American College of Rheumatology (ACR) Pediatric response at 6 months, patients were divided in four mutually exclusive groups: (1) non-responders, (2) responders at 30%, (3) responders at 50%, and (4) responders at 70%. The long-term outcome in each response group was evaluated by calculating the percentage change in active and restricted joint counts from baseline to 1, 2 and 5 years and the frequency of inactive disease at 5 years. RESULTS: At 6 months, 42 patients were classified as non-responders, 24 as 30% responders, 26 as 50% responders, and 33 as 70% responders. Patients who had achieved a 70% response showed a significantly greater percentage improvement in active joint count between baseline to 5 years compared with non-responders and 30% responders, and a significantly greater percentage improvement in restricted joint count between baseline to 5 years compared with 30% responders. The 70% responders also had a greater frequency of inactive disease at 5 years compared with 30% responders, CONCLUSIONS: Our results show that the achievement of an ACR Pediatric 70 response at 6 months after start of MTX therapy predicts a more favorable long-term outcome of patients with JIA.

A longitudinal analysis of physical functional disability over the course of juvenile idiopathic arthritis.

OBJECTIVE: To describe the longitudinal course of physical functioning in children with juvenile idiopathic arthritis (JIA) and identify predictors of long-term functional impairment. METHODS: Between January 1987 and December 2002, 227 patients had two or more functional ability questionnaires completed by a parent. The total number of questionnaires was 1356 and the follow-up between first and last questionnaire administration was 949.7 patient years. At each questionnaire administration, patients were assigned to one of three functional disability states (1 = no disability; 2 = mild to moderate disability; 3 = severe disability), based on their functional ability score. Predictor variables included sex, onset age, JIA category, age at visit, disease duration, presence of antinuclear antibodies, joint counts, acute phase reactants and initial disability state. RESULTS: Despite patient variability in the course of physical functioning, the following three longitudinal patterns were observed: (1) a stable state of disability throughout the entire study period, with continued absence of disability in 27.8% of patients and persistently moderate disability in 3.5% of patients; (2) a steady improvement (22.9% of patients) or deterioration (5.7% of patients) in disability over time; (3) a fluctuating course of disability, with deterioration and improvement (40.1% of patients). Younger age at disease onset and a greater restricted joint count were the strongest predictors of long-term functional impairment. CONCLUSION: A wide within-patient and between-patient variability in the longitudinal course of functional disability was found. Children with early disease onset and a greater number of restricted joints had the highest risk of developing long-term physical disability.

Oxaliplatin combined with 5-fluorouracil and methotrexate in advanced colorectal cancer.

BACKGROUND: A promising regimen including 5-Fluorouracil, methotrexate and oxaliplatin is reported. PATIENTS AND METHODS: Patients with untreated measurable metastatic disease received bolus 5-Fluorouracil (600 mg/m2) on days 2 and 16, modulated by methotrexate (200 mg/m2) 24 h earlier, alternated with 4 weeks of continuous infusion of 5-Fluorouracil (200 mg/m2/daily) plus oxaliplatin (130 mg/m2) on days 29 and 56, followed by 2 weeks of rest. Serum vascular endothelial growth factor (VEGF) was analyzed at baseline and before every cycle. RESULTS: Fifty-eight patients were enrolled. Objective remissions were reported in 45.6% (95% CI=34.3%, 57.3%). The median progression-free survival was 7.8 months and the median overall survival was 19.4 months. No grade 4 toxicity was reported, except for one case of diarrhea. The serum VEGF evaluated in 23 patients showed a decreasing trend during therapy. CONCLUSION: The regimen was active, well tolerated and may be a possible option in patients not suitable for radical surgery.

Weighting improves the information provided by joint counts on the severity of arthritis and its impact on patients' well-being in juvenile idiopathic arthritis.

OBJECTIVE: To develop a scoring system for juvenile idiopathic arthritis (JIA) in which joints are weighted to reflect their relative importance to children's function and to examine whether weighting increases the correlation of joint counts with subjective and laboratory outcome measures. METHODS: A weighted joint score was devised by a panel of experienced paediatric rheumatologists, who assigned a weight from 1 (not very important) to 10 (essential for key functional activities) to each joint based on its functional importance to children's physical and daily activities. The associations of simple and weighted counts of swollen, tender, limited and active joints with the physician's global assessment of overall disease activity, the parent's global assessment of the child's overall well-being and intensity of pain, the Childhood Health Assessment Questionnaire (C-HAQ), the Child Health Questionnaire (CHQ) and the erythrocyte sedimentation rate were compared using Spearman's correlation analysis in 60 unselected patients seen in the clinic and in 61 consecutive patients with disease duration > or = 5 yr. RESULTS: Weighted counts of swollen and active joints yielded greater correlation with the physician's global assessment than did simple counts. The correlation of weighted counts of swollen, painful and active joints with the parent's assessment of overall well-being and intensity of pain was superior to that provided by simple counts. Weighting increased most of the correlations between joint counts and the C-HAQ score and the physical component of the CHQ. CONCLUSION: Weighting improves the information provided by joint counts on the severity of arthritis and its impact on patients' well-being.

Responsiveness of clinical measures to flare of disease activity in juvenile idiopathic arthritis.

OBJECTIVE: To compare the responsiveness of clinical measures in the assessment of disease flare in patients with juvenile idiopathic arthritis (JIA). METHODS: The clinical records of all consecutive patients with JIA who were diagnosed between 1995 and 2000 were retrospectively reviewed. In each patient, all visits made during follow-up were analyzed and those meeting the criteria for disease flare were recorded. The definition of flare was based on the therapeutic alterations made by the attending physician. Responsiveness of JIA clinical measures to relevant increase in disease activity (a flare) was evaluated by assessing the score change of each measure from a visit made 6 (+/- 3) months before a flare and the flare visit. Responsiveness statistics included the standardized response mean (SRM) and the effect size (ES). RESULTS: A total of 115 patients, who were followed for 0.5 to 6.2 years (mean 2.8 years), were studied. During follow-up, 51 patients (44%) experienced 1 or more disease flares, with the total number of flares being 75. Strong responsiveness (ES and SRM > or = 0.8) to increase in disease activity was demonstrated by the physician's and parent's global assessments, the global articular severity score, and the morning stiffness. The active, swollen and painful joint counts, the swelling, pain on motion/tenderness and limited range of motion (LROM) scores, and the erythrocyte sedimentation rate revealed moderate responsiveness (ES and SRM > or = 0.5). The poorest performances (ES and/or SRM < 0.5) were provided by the parent's assessment of pain, the functional ability tool, the number of joints with LROM, the LROM score, the C-reactive protein, the white blood cell and platelet count, and the hemoglobin level. CONCLUSION: Our analysis suggests that the swollen or painful joint counts are better suited than the count of joints with LROM for the assessment of disease flare in patients with JIA.

Relative responsiveness of condition specific and generic health status measures in juvenile idiopathic arthritis.

OBJECTIVES: To compare the relative responsiveness of condition specific measures with that of a generic health status instrument for outcome assessment of intra-articular corticosteroid (IAC) injection in patients with juvenile idiopathic arthritis (JIA). METHODS: We examined 44 consecutive patients with oligoarticular JIA before an IAC injection and after 6 months. Condition specific measures included physician's and parent's global assessments, the Childhood Health Assessment Questionnaire (CHAQ), the articular indices, and laboratory indicators of systemic inflammation. The generic health status instrument was the Child Health Questionnaire (CHQ), which was divided into two parts: the physical score (PhS) and the psychosocial score (PsS). Responsiveness statistics were the standardised response mean, the effect size, and Guyatt's method. The discriminative ability of the clinical measures in distinguishing improved from non-improved patients was evaluated with the correlation and the receiver operating characteristic methods, using the physician's and the parent's judgements of the treatment outcome as external criteria. RESULTS: All responsiveness statistics and discriminative ability assessments consistently ranked the physician's global assessment of the disease activity as the most responsive measure. The CHQ-PhS revealed superior ability in detecting baseline versus 6 month change compared with the CHAQ and the CHQ-PsS; both summary scales of the CHQ revealed better discriminative ability than the CHAQ. CONCLUSIONS: The physician's global assessment of the disease activity proved the most responsive outcome measure in our patients with JIA. The relative evaluative properties of the generic health status instrument and the CHAQ should be further investigated.

Unilateral destructive wrist synovitis in juvenile idiopathic arthritis.

OBJECTIVE: To describe the clinical and radiographic features of a group of juvenile idiopathic arthritis (JIA) patients who developed unilateral destructive wrist synovitis. METHODS: All wrist radiographs performed yearly between 1986 and 2002 in JIA patients who had wrist involvement were retrospectively reviewed to identify patients who had unilateral erosive wrist synovitis, defined as a difference of at least -3 units in the Poznanski score between the affected wrist and the unaffected wrist, with the Poznanski score in the unaffected wrist being > -2 units throughout the follow-up period. Clinical and radiographic data obtained during follow-up were recorded for all patients. RESULTS: Of a total of 250 patients for whom we had approximately 900 wrist radiographs, 6 patients were found to have unilateral erosive wrist synovitis. The JIA onset subtype was oligoarticular in 5 patients and polyarticular in 1 patient and the disease duration from presentation to the last follow-up visit ranged from 2 to 16 years. The arthritis course was polyarticular in all patients. Five patients had positive antinuclear antibodies (ANA) and 1 had positive rheumatoid factor (RF). At the last follow-up visit, all patients had some impairment of wrist function and 2 patients had wrist subluxation. There was a marked radiographic damage in all affected wrist, with the Poznanski ranging from -8.0 to -8.50 units in 3 patients and being -5.5, -3.1 and -2.4 units, respectively, in 3 patients. The severity of radiographic damage in the ANA-positive patients with the longest disease duration was comparable to that observed in the RF-positive patient. CONCLUSION: Unilateral erosive wrist synovitis seems to be uncommon in JIA. Patients with unilateral wrist synovitis may be at risk of a destructive course irrespective of the JIA onset subtype.

Combination therapy with methotrexate and cyclosporine A in juvenile idiopathic arthritis.

OBJECTIVE: To investigate the efficacy and safety of a combination therapy with methotrexate (MTX) and cyclosporine A (CyA) in patients with juvenile idiopathic arthritis (JIA) who were refractory to MTX as a single second-line agent. METHODS: Seventeen consecutive patients with JIA who had refractory polyarthritis despite a minimum of 6 months of MTX as a single second-line agent at the dose of 15 to 25 mg/m2/week were continued with MTX with the addition of CyA (4 mg/kg/day) for 6 to 30 months (median 10 months) were analyzed. The clinical response to therapy was assessed through the preliminary definition of improvement in JIA. RESULTS: At the end of the treatment, as compared to the time when CyA was added to MTX, 8 patients (47%) met the 30% definition of improvement; among them 5 (29%) met the 70% definition of improvement, and 2 (12%) achieved complete disease control. Seven patients (41%) experienced side effects: 4 gastrointestinal discomfort, 1 liver transaminase elevation, and 2 increase > or = 30% in the serum creatinine concentration. No patients was discontinued from combination therapy due to adverse events. CONCLUSION: In our JIA patients who were refractory to MTX as a single second-line agent, the addition of CyA was associated with a significant clinical improvement in roughly half of the patients.

Factors affecting the efficacy of intraarticular corticosteroid injection of knees in juvenile idiopathic arthritis.

OBJECTIVE: To determine in a prospective analysis whether baseline demographic, clinical, and laboratory variables predict the outcome of intraarticular corticosteroid (IAC) injection of the knees in children with juvenile idiopathic arthritis (JIA). METHODS: We studied consecutive patients who met the criteria for the diagnosis of JIA and received their initial injection of triamcinolone hexacetonide in one or both knees. Predictor variables included sex, age, age at onset of JIA, onset subtype, disease duration, drug therapy at the time of IAC injection, physician and parent global assessment of disease status, Childhood Health Assessment Questionnaire disability index, erythrocyte sedimentation rate (ESR), C-reactive protein, involvement of other joints besides knees, amount of fluid aspirated, and dose of IAC injected. The primary outcome measure was persistence of complete clinical response at 6 months, i.e., no evidence of synovitis clinically. RESULTS: Ninety-four patients were available for analysis. At 6 months after the IAC injection, 65 (69%) patients showed a sustained complete clinical response, whereas 29 (31%) had had a recurrence of joint inflammation. Univariate statistical analyses showed that patients who had a sustained clinical response had a significantly higher ESR than those who did not (p = 0.023). The ESR was the only variable that remained in the best-fit model from multivariate logistic regression analysis (OR 2.61, p = 0.049). CONCLUSION: Our findings indicate that patients with JIA who have a higher ESR are more likely to benefit from IAC injection of the knees.