Mitigation of gaseous emissions from dairy livestock: A farm-level method to examine the financial implications.

Feeding the world's population while minimising the contribution of agriculture to climate change is one of the greatest challenges facing modern society. This challenge is particularly pronounced for dairy production where the carbon footprint of products and the mitigation costs are high, relative to other food stuffs. This paper reviews a number of mitigation measures that may be adopted by dairy farmers to reduce greenhouse gas emissions from their farms. A simulation model is developed to assess the cost-benefit of a range of mitigation measures. The model is applied to data from Ireland, a country with a large export-oriented dairy industry, for a range of farms including top, middle and bottom performing farms from a profitability perspective. The mitigation measures modelled included animal productivity, grass production and utilisation, better reproductive performance, early compact calving, reduced crude protein, decreased fertiliser N, protected urea, white clover, slurry tank cover and low emission slurry spreading (LESS). The results show that over half of the greenhouse gas abatement potential and most of the ammonia abatement potential were realised with cost-beneficial measures. Animal and feed-related measures that increased efficiency drove the abatement of GHG emissions. Low-emission slurry spreading was beneficial for the bottom and middle one-third of farms, while protected urea and reducing nitrogen use accounted for most of the ammonia abatement potential for the most profitable farms. Results showed that combining mitigation measures resulted in a decrease of 23%, 19%, and 12% in GHG emissions below 2020 levels for the bottom, middle, and top performing dairy farms, respectively. The findings imply that top dairy farms, that are already managed efficiently and optimally, may struggle to achieve the national and international GHG reduction targets with existing technologies and practices.

Preliminary insights into RNA in CSF of pediatric SMA patients after 6 months of nusinersen.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare autosomal-recessive neurodegenerative disorder caused by mutations in survival motor neuron 1 (SMN1) gene, and consequent loss of function of SMN protein, which results in progressive loss of lower motor neurons, and muscular wasting. Antisense oligonucleotide (ASO) nusinersen (Spinraza®) modulates the pre-mRNA splicing of the SMN2 gene, allowing rebalance of biologically active SMN. It is administered intrathecally via lumbar puncture after removing an equal amount of cerebrospinal fluid (CSF). Its effect was proven beneficial and approved since 2017 for SMA treatment. Given the direct effect of nusinersen on RNA metabolism, the aim of this project was to evaluate cell-free RNA (cfRNA) in CSF of SMA patients under ASOs treatment for biomarker discovery. METHODS: By RNA-sequencing approach, RNA obtained from CSF of pediatric SMA type 2 and 3 patients was processed after 6 months of nusinersen treatment, at fifth intrathecal injection (T6), and compared to baseline (T0). RESULTS: We observed the deregulation of cfRNAs in patients at T6 and we were able to classify these RNAs into disease specific, treatment specific and treatment dependent. Moreover, we subdivided patients into "homogeneous" and "heterogeneous" according to their gene expression pattern. The "heterogeneous" group showed peculiar activation of genes coding for ribosomal components, meaning that in these patients a different molecular effect of nusinersen is observable, even if this specific molecular response was not referable to a clinical pattern. CONCLUSIONS: This study provides preliminary insights into modulation of gene expression dependent on nusinersen treatment and lays the foundation for biomarkers discovery.

Treatment of recurrent pilonidal cysts with nd-YAG laser: report of our experience.

PURPOSE: Surgical treatment remains the first-line therapy of pilonidal cyst but is associated with high levels of postoperative pain, adverse events and a recurrence rate of 30%. We report our experience with laser hair removal using the Nd-YAG laser for the treatment of pilonidal cyst. MATERIALS AND METHODS: Ten patients affected by pilonidal cyst were examined and treated from October 2011 to November 2016. Treatments were carried out using the Nd-YAG laser (Deka M.E.L.A, Calenzano, Florence, Italy) at a wavelength of 1064 nm at 30-day interval. RESULTS: Nine patients were asymptomatic after the second treatment, while in one case the symptom disappeared after the fourth session. After 4-8 treatments, the pilonidal cyst had clinically disappeared and patients subjectively felt healed. In all cases, the soft-tissue ultrasounds performed before the first and after the last session showed the disappearance of the pilonidal cyst. In the follow-up, all the patients remained asymptomatic without any disease recurrence. CONCLUSIONS: Nd-YAG laser is an effective treatment for pilonidal cysts, providing excellent results with quick healing and no risk of serious adverse side-effects. It could be a very attractive alternative to open surgery, enabling patients to prevent the frequent and severe postoperative issues associated with surgery.

Adult Onset Vitiligo: Multivariate Analysis Suggests the Need for a Thyroid Screening.

Background. There are limited epidemiological studies evaluating the effect of age at onset on disease features in vitiligo. Objectives. To identify factors associated with adult onset vitiligo in comparison with childhood onset vitiligo. Patients and Methods. We retrospectively collected medical records of 191 patients. Such records included clinical examination, personal and familial medical history, laboratory evaluations, concomitant vitiligo treatment and drug assumption. Results. 123 patients with a disease onset after the age of 40 (adult onset vitiligo) were compared with 68 patients who developed vitiligo before the age of 12 (childhood onset vitiligo). Multivariate analysis revealed that personal history of thyroid diseases (P = 0.04; OR 0.4), stress at onset (P = 0.002; OR = 0.34), personal history of autoimmune thyroid disease (ATD) (P = 0.003; OR = 0.23), and thyroid nodules (P = 0.001; OR 0.90) were independently associated with adult onset vitiligo, whereas family history of dermatological diseases (P = 0.003; OR = 2.87) and Koebner phenomenon (P < 0.001; OR = 4.73) with childhood onset vitiligo. Moreover, in the adult onset group, concomitant thyroid disease preceded vitiligo in a statistically significant number of patients (P = 0.014). Conclusions. Childhood onset and adult onset vitiligo have different clinical features. In particular, ATD and thyroid nodules were significantly associated with adult onset vitiligo, suggesting that a thyroid screening should be recommended in this group of patients.

High prevalence of circulating autoantibodies against thyroid hormones in vitiligo and correlation with clinical and historical parameters of patients.

BACKGROUND: Autoantibodies against thyroid hormones (THAbs) directed towards triiodothyronine (T3-Ab) and/or thyroxine (T4-Ab) are very rare in the general population. They are increased in some nonthyroidal autoimmune diseases, where they seem to predict autoimmune thyroid disorders (ATDs). So far, their presence in patients with vitiligo has not been evaluated, but it might have a possible predictive role. OBJECTIVES: To assess the prevalence of THAbs in a group of vitiligo patients and to correlate their presence with clinical and historical parameters. METHODS: In total 79 patients with nonsegmental vitiligo and 100 controls were examined. Clinical characteristics of vitiligo and family and personal medical history were evaluated. Antinuclear autoantibodies, thyroid hormones and thyroid autoantibodies were measured. IgM T3-Ab, IgG T3-Ab, IgM T4-Ab and IgG T4-Ab were assayed by a radioimmunoprecipitation technique. Fisher's test, Student's t-test and χ(2)-test were used for statistical analysis. RESULTS: Overall 77 of 79 patients (97%) had at least one type of THAb (11 T3-Ab, 10 T4-Ab, 56 both). In the control group, only one person (1%) had THAbs. In patients with vitiligo, T3-Abs were significantly associated with leucotrichia (IgM+IgG, P = 0.033; IgG, P = 0.039; IgM, P = 0.005) and thyroglobulin autoantibodies (IgM+IgG, P = 0.031; IgG, P = 0.058), while the absence of T3-Ab was related to personal history of cancer (IgM+IgG, P = 0.021; IgG, P = 0.039). T4-Abs were significantly associated with vitiligo activity (IgM+IgG, P < 0.001; IgM, P = 0.037) and duration (IgG, P = 0.013). CONCLUSIONS: The surprisingly high prevalence of THAb in patients with vitiligo and their associations suggest a possible pathogenetic role in the disease and stress the tight link between vitiligo and ATDs. Further evaluation in a larger group of patients and an adequate follow-up are needed to define their potential predictive role.

Non-segmental vitiligo and psoriasis comorbidity - a case-control study in Italian patients.

BACKGROUND: A recent systematic evaluation of vitiligo and psoriasis comorbidity has not yet been reported in a large series of patients with vitiligo. OBJECTIVE: To investigate the practical/clinical implications in subjects with both vitiligo and psoriasis compared to those with vitiligo alone. METHODS: This was a case-control study on 463 vitiligo patients in our clinic from March 2008 to April 2011. Medical assessment was performed by dermatologists using the modified Vitiligo European Task Force form. RESULTS: In an univariate analysis, inflammation/pruritus [odds ratio (OR) 2.42, P = 0.03], use of drugs that can induce psoriasis (OR 2.74, P = 0.01), a family history (FH) of psoriasis (OR 2.87, P = 0.02), cardiovascular disease (OR 5.70, P = 0.001), hypertension (OR 4.7, P = 0.006) and type 2 diabetes mellitus (OR 3.87, P = 0.004), were significantly correlated with patients exhibiting vitiligo and psoriasis comorbidity. A trend was found in personal history of cardiovascular disease in patients with both diseases (OR 2.99, P = 0.07). FH of vitiligo was significantly associated with patients having only vitiligo (OR 0.35, P = 0.05). Multivariate analysis demonstrated that inflammation/pruritus in vitiligo macules (OR 2.56, P = 0.047) and a FH of cardiovascular disease (OR 4.07, P = 0.02) were the most significant predictors of patients having both psoriasis and vitiligo, while the presence of organ-specific autoantibodies (OR 0.24, P = 0.007) was significantly associated with patients having only vitiligo. CONCLUSION: The presence of vitiligo and even mild psoriasis is significantly correlated with a family history of cardiovascular disease, a factor that requires greater attention and follow-up with respect to that necessary for vitiligo patients.

Autoimmune signals in non-segmental vitiligo patients are associated with distinct clinical parameters and toxic exposures.

BACKGROUND: Although non-segmental vitiligo is commonly considered an autoimmune disease, the possible differences between non-segmental vitiligo patients with and without autoimmune signals have not been clearly established. OBJECTIVE: To perform a comparison of non-segmental vitiligo patients with autoimmune signals (AIS) vs. those without autoimmune signals (NAIS) in regards to clinical characteristics and toxic/drug exposure. METHODS: 112 vitiligo patients were selected for a sex and age matched (1 : 1) case control study at an university based dermatology outpatient hospital specialized in pigmentary disorders. Medical assessment was performed by dermatologists using the modified Vitiligo European Task Force form and serological and clinical signs of autoimmunity were evaluated. RESULTS: Disease duration, age of onset, patient history of cardiovascular disease, past smoking history, use of drugs, and consummation of goitrogenic foods were all significantly increased in the AIS group using McNemar's test for matched pairs. In our conditional regression model, the simultaneous presence of disease duration, use of prescription drugs, and consummation of goitrogenic foods were the best predictors of AIS vitiligo patients. CONCLUSION: The evaluation of non-segmental vitiligo patients according to the presence vs. the absence of autoimmune signals allows us to correlate patients exhibiting autoimmune phenomenon with certain clinical characteristics, namely long disease duration, use of prescription drugs, and consumption of goitrogenic substances. In the presence of the aforementioned clinical profile, we suggest an evaluation of autoimmune signals.

"Zeus" a new oral anticoagulant therapy dosing algorithm: a cohort study.

The demand for oral anticoagulant therapy (OAT) has constantly increased during the last ten years with an extended use of computer assistance. Many mathematical algorithms have been projected to suggest doses and time to next visit for patients on OAT. We designed a new algorithm: "Zeus". A "before-after" study was planned to compare the efficacy and safety of this algorithm dosing OAT with manual dosage decided by the same expert physicians according to the target of International Normalized Ratio (INR). The study analysed data of 1876 patients managed with each of the two modalities for eight months, with an interval of two years between them. The aim was to verify the increased quality of therapy by time spent in INR target and efficiency and safety of Zeus algorithm. Time in therapeutic range (TTR) was significantly (p < 0.0001) higher during the algorithm dosing period in comparison with the TTR during manual management period (62.3% vs 50.3%). The number of PT/INR tests above 5 was significantly (p < 0.001) reduced by algorithm suggested prescriptions in comparison with manual those (254 vs 537 times). The anticoagulant drug amount prescribed according to the algorithm suggestions was significantly (p < 0.0001) lower than that of the manual method. The number of clinical events observed in patients during the algorithm management time was significantly (p < 0.05) lower than that in those managed with the manual dosage. This study confirms the clinical utility of the computer-assisted OAT and shows the efficacy and safety of the Zeus algorithm.

Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors.

BACKGROUND: This trial sought to examine the effects of high dosage of folic acid and vitamin C supplementation on red blood cell folate (RCF), serum folate (SF) and homocysteine (Hcy) levels in subjects who smoke more than 15 cigarettes per day. METHODS: A prospective study of 100 Italian repeat blood donors was undertaken to measure RCF, SF and Hcy levels before and after 45 days of vitamin supplementation. All subjects were randomised into four groups: [A] folic acid (FA) 5 mg/day, [B] vitamin C 500 mg/day, [C] FA 5 mg/day plus vitamin C 500 mg/day [D] no supplementation. RESULTS: Before supplementation the median RCF, SF and Hcy levels were similar in the four groups; 32 (40%) subjects had an RCF level below 340 nmol/l, 15 (18.8%) had an SF level below 6.8 nmol/l and 21 (26.3%) had an Hcy level above 16 micromol/l. After 45 days the median RCF and SF levels were significantly (P<0.01) increased in all supplemented subjects. The median Hcy level was significantly (P=0.008) reduced in subjects supplemented with FA and significantly (P=0.01) increased in those supplemented with vitamin C alone. CONCLUSION: The supplementation with 5 FA mg/day is able to increase significantly both RCF and SF levels and reduce Hcy level in Italian smoker-blood donors.

ProC global: a new automated screening assay for the evaluation of total function of the protein C system.

Protein C (PC) pathway represents a major physiologic inhibitory mechanism regulating the coagulation cascade. A new automated functional screening assay (ProC Global) for the evaluation of the PC-system was tested to define its ability to identify patients with known inherited defects such as factor V (FV) Leiden mutation and PC and protein S (PS) deficiency. A total of 249 patients who were symptomatic or asymptomatic for previous venous thromboembolism (VTE) were evaluated, 50 of whom had FV Leiden mutation, 36 had PC deficiency, and 34 had PS deficiency. One hundred healthy subjects were also tested, as well as 40 blood donors of both sexes in whom coagulation abnormalities were not found. Results of ProC Global test were expressed as normalized ratio (NR) and values below an established cut-off level were consistent with a positive test. ProC Global was positive in all 50 patients with the FV Leiden mutation (mean NR = 0.59; range, 0.37 to 0.69). ProC Global correctly identified 32 of 36 (89%) PC defects (mean NR = 0.63; range, 0.34 to 1.21) and 25 of 34 (73.5%) PS defects (mean NR = 0.76; range, 0.5 to 1.23). Overall, 92.5% of hereditary defects of the PC system considered in this study were identified by ProC Global test. ProC Global exhibited NR above cut-off level in all 40 blood donors without coagulation defects. ProC Global is a new automated screening test with some diagnostic potential in identifying patients with defects of the PC system. However, ProC Global in its current form cannot substitute the assay of each single component of this inhibitory system in the daily screening for thrombophilia.

As compared to kaolin clotting time, silica clotting time is a specific and sensitive automated method for detecting lupus anticoagulant.

Lupus anticoagulants (LAs) are antiphospholipid antibodies capable of interfering with the coagulation system and modifying in vitro the phospholipid-dependent clotting tests. Colloidal silica was used as activator to perform an activated partial thromboplastin time (aPTT) in 73 plasma samples with pathologically elevated kaolin clotting time (KCT) values using a photooptical automated coagulometer. Samples were incubated for 5 min with micronized silica, and after recalcification, the clotting times were measured. Pathologically prolonged results were confirmed by a confirmation and a neutralization test adding platelet-poor normal plasma (PPNP) and natural phospholipids, respectively. Silica clotting time (SCT) was abnormally elevated in 72/73 (98.6%) (mean ratio 1.71 +/- 0.28) KCT positive samples and normalized (mean ratio 1.03 +/- 0.16) after adding natural phospholipids to test plasma. The values expressed as SCT and KCT ratios were significantly correlated (r = .92; P < .001). SCT was normal in 40 healthy subjects utilised as controls (mean ratio 0.99 +/- 12). Sensitivity, specificity and diagnostic accuracy of SCT were 98.6%, 100% and 97.6%, respectively. Our data suggest that SCT is a sensitive test for detecting LA with a prolonged KCT in automated photooptical coagulometers. This peculiarity makes it particularly useful, in combination with diluted Russel viper venom time (dRVVT), for large-scale screening tests on LA.

Neutropenic enterocolitis in patients with acute leukemia: prognostic significance of bowel wall thickening detected by ultrasonography.

PURPOSE: Neutropenic enterocolitis (NE) is a severe complication of intensive chemotherapy and is barely identifiable by clinical signs alone. Ultrasonography (US) supports the diagnosis of NE by showing pathologic thickening of the bowel wall. The aim of this study was to evaluate the prognostic value of the degree of mural thickening evaluated by US in patients with clinically suspected NE. PATIENTS AND METHODS: Neutropenic patients with fever, diarrhea, and abdominal pain after intensive chemotherapy for hematologic malignancies were studied with abdominal US. We evaluated the degree of bowel wall thickening detected by US and its correlation with the duration of the clinical syndrome as well as NE-related mortality. RESULTS: Eighty-eight (6%) of 1,450 consecutive patients treated for leukemia had clinical signs of NE. In 44 (50%) of 88 patients, US revealed pathologic wall thickening (mean +/- SD, 10.2 +/- 2.9 mm; range, 6 to 18). The mean duration of symptoms was significantly longer in this group (7.9 days) than among patients without mural thickening (3.8 days, P <.0001), and the NE-related mortality rate was higher (29.5% v 0%, P <.001). Patients with bowel wall thickness of more than 10 mm had a significantly higher mortality rate (60%) than did those with bowel wall thickness < or = 10 mm (4.2%, P <.001). CONCLUSION: Symptomatic patients with sonographically detected bowel wall thickening have a poor prognosis compared with patients without this finding. In addition, mural thickness of more than 10 mm is associated with poorer outcome among patients with NE.

Folate status in Italian blood donors: relation to gender and smoking.

BACKGROUND AND OBJECTIVES: Folate deficiency in the general population is associated with a risk of cardiovascular disease and various cancers. The aim of this study was to evaluate folate status in Italian blood donors and its relationship with gender and smoking habit. DESIGN AND METHODS: A prospective study of 201 first visit donors (99 males and 102 females) was undertaken to evaluate folate status by measuring serum folate (SF) and red blood cell folate (RCF) levels and relating those with gender and smoking habit (100 smokers and 101 non-smokers). RESULTS: The rates of SF level less than 6.8 nmol/L and RCF less than 340 nmol/L were 9.9% and 25.3%, respectively in Italian blood donors. Mean RCF level was significantly lower (p<0.05) in females than in males and in smokers compared to non-smokers (p<0.001). The risk of reduced RCF levels in smokers was related to the number of cigarettes smoked per day, more than nine cigarettes increased the relative risk (RR) of low RCF level to 2.93 (95% C.I.: 1.34-6.41). INTERPRETATION AND CONCLUSIONS: This study suggests that folate deficiency, evaluated by RCF and SF levels, is widespread in Italian blood donors. Moreover, RCF values seem related to gender in non-smokers and modified by smoking habit, according to the cigarettes number smoked per day.

The role of high resolution pulsed and color Doppler ultrasound in the differential diagnosis of benign and malignant lymphadenopathy: results of multivariate analysis.

BACKGROUND: The role of high resolution pulsed and color Doppler ultrasound in the differential diagnosis of benign and malignant lymphadenopathy is still unclear. METHODS: High resolution pulsed and color Doppler ultrasound was used prospectively to investigate superficial lymph node enlargement in 71 patients undergoing surgical biopsy at the onset of lymphadenopathy. The aim of this study was to define, in multivariate analysis, the ultrasonographic parameters useful in the differential diagnosis of benign and malignant lymphadenopathy. RESULTS: Volume, vascularization score, pulsatility index, and resistive index were significantly higher in the 53 malignant lymph nodes studied than in the 18 benign lymph nodes studied. The long-to-short axis ratio was significantly lower in neoplastic lymph nodes than in reactive lymph nodes. Stepwise logistic regression selected only the long-to-short axis ratio and the vascularization score as parameters that independently and significantly contributed to the differentiation of neoplastic from reactive lymph nodes. The diagnostic efficiency of the combined criteria evaluated by the area under the receiver operating characteristic curve was 0.8339. CONCLUSIONS: High resolution pulsed and color Doppler ultrasound may provide information that is useful in making correct differential diagnoses of malignant or benign lymphadenopathy.

HIV-HCV RNA loads and liver failure in coinfected patients with coagulopathy.

BACKGROUND AND OBJECTIVE: The aim of this study was to measure contemporaneously HCV-RNA load, HIV-RNA load and CD4+ lymphocyte count in HCV/HIV coinfected patients with coagulopathy and to examine the relationship between these parameters and the liver failure. DESIGN AND METHODS: A cross-sectional study was performed on 54 patients with severe coagulopathy: 39 HCV/HIV coinfected and 15 HCV+/HIV- comparable for age and HCV exposure time. HCV-RNA and HIV-RNA load, CD4+ lymphocyte count, biochemical and ultrasonographic parameters were evaluated at the time of entry to the study. RESULTS: Mean HCV-RNA load was significantly higher in coinfected patients (643,872 717,687 copies/mL) than in HCV+/HIV- (mean 161,573 276,896 copies/mL) (p = 0.01). The 39 HCV/HIV coinfected patients had a mean HIV-RNA load of 205,913 456,311 copies/mL (range 4,000-2,500,000) and a mean CD4+ lymphocyte count of 206.5171/microL (range 5-693). Five of the 39 (12.8%) coinfected patients had liver failure. In these five patients the mean HCV-RNA load (770,200 996,426 copies/mL) was high but not significantly different from that in the 34 HCV+/HIV+ patients (623,496 682,239 copies/mL) without liver failure (p = 1.0). Coinfected patients with liver failure had a significantly higher HIV-RNA load (mean 764, 599 978,542 copies/mL) and lower CD4+ lymphocyte count (mean 52.655. 6/microL) than those observed in coinfected patients without liver failure (p = 0.007 and p = 0.03, respectively). A significant inverse correlation was found between CD4+ lymphocyte count and HIV-RNA load (r = -0.37, p = 0.01). INTERPRETATION AND CONCLUSIONS: HCV-RNA load is significantly higher in HIV+ than in HIV- patients with coagulopathy. Liver failure was found only in the HCV/HIV coinfected patients with severe immunodepression, expressed either by low CD4+ lymphocyte count or by high HIV-RNA load.