Decapitation of an agricultural worker by a combine harvester: a case report.

Background: Each year, there are billions of agricultural work accidents involving the operation of tractors, grain augers, harvest combines, power take-off devices, or balers and thrashers. Field accidents of this nature seem more common on afternoons, just as road accidents tend to skew toward nighttime. The lesions can vary widely and depends strictly on the operation of the machinery analyzed. Aims: This paper aims to present a peculiar case of decapitation by a combine harvester, showing how, in cases of injury due to agricultural machinery, it is fundamental a correct execution of a scene investigation, autoptic examination, and cooperation with a specialist in engineering. Case Report: A 54-year-old man was found decapitated on the header of a combine harvester; his extremities were also dismembered. At autopsy, a clean oblique cut across the first cervical vertebra had severed the head at the neck. Although the right arm remained intact, both lower extremities were mutilated, showing numerous exposed and open fractures. A bleeding, penetrating wound to the back was additionally noted. In the days that followed, missing parts (head and left leg) were discovered in other machine components (grain tank and straw walker, respectively). All observed injuries were compatible with the mechanics of the cochlea, its rotating movement inflicting the damages above. Collaboration between pathologists and engineers was fundamental to recreating the dynamics of this rare decapitation accident by a combine harvester.

Death by artery injury: two peculiar cases of sharp force fatality.

Background: As sharp force injury accounts for 10-20% of clinical forensic examinations, forensic pathologists are often asked to investigate deceased victims of stab wounds. Moreover, homicide by sharp force (stabbing) is one of the most common in European countries, involving generally domestic or interpersonal conflict. Stabbing as a suicide method constitutes a low percentage of all suicides, 2% to 3%. Accidental death due to sharp force is even rarer (0-3%) and usu-ally caused by an impact or a fall into different type of glass surface. Death due to stabbing is usually caused by exsanguinating incisions to organs or large blood vessels (such as arteries), leading to haemor-rhagic shock. Penetrating artery injuries are well known in clinical settings, and extremities are the most common sites of such injuries. Indeed, 50% to 60% of injuries occur in femoral or popliteal arteries, 30% in brachial artery. Aims: The aim of this paper is to present two rare cases of sharp force fatality, showing how a thorough forensic pathology methodology, including death scene investigation, autopsy examination, and toxicological analyses, are pivotal to detect the manner of death. Case Reports: This paper presents two peculiar cases of sharp force fatalities: the first, a single and accidental stab injury on the right armpit which caused a complete transection of the axillary artery; the second, a single homicidal stab wound on the lower leg causing a full-thickness lesion of the anterior tibial artery.

Vitamin D status of inmates: the experience of penitentiaries prisons in the province of Salerno in Southern Italy.

Introduction: Prisoners are at risk of developing vitamin D deficiency due to their lacking exposure to sunlight. So far, there are no published studies evaluating blood levels of vitamin D in relation to the health status of inmates and the quality of the Italian prison system. Aim: To investigate vitamin D status and its determinants in a cohort of prisoners. Subject and Methods: One hundred and seventy-two (172) pri-son inmates (males, n=159, age 47± 11.3 years; females, n=13, age 43.91±12.18 years) of three penitentiaries in the province of Salerno. Vitamin D deficiency, insufficiency and sufficiency were respectively defined as a 25(OH)D level <20 ng/mL; from 20 to 30 ng/mL, >30 ng/mL. Results: In our group, Vitamin D deficiency occurs in 77.32% of the prisoners with 32.55% of the cases having severe insufficiency. Prisoners with higher BMI show lower circulating vitamin D levels (p<0.001). No significant relationship was found with the duration of detention (Pearson R: 0.01). Conclusion: In this cohort of inmates the vitamin D status is determined by BMI, but not by the duration of the detention.

First-line daratumumab shows high efficacy and tolerability even in advanced AL amyloidosis: the real-world experience.

BACKGROUND: Daratumumab was the first monoclonal CD38 antibody with single-agent activity approved for the treatment of multiple myeloma. Moreover, daratumumab demonstrated high response rates in relapsed immunoglobulin light-chain (AL) amyloidosis. PATIENTS AND METHODS: In our single-center retrospective real-life case series, we analyzed the efficacy and safety of daratumumab as first-line treatment. Daratumumab was administered with low-dose dexamethasone alone or in combination with other multiple myeloma therapeutics RESULTS: Fourteen patients were eligible, including nine patients with cardiac stage IIIa or IIIb. Overall hematologic response rate was 100%, with 64.3% achieving complete response after a median of 16 cycles of treatment. Median time to hematologic response was 1.4 months. Organ response rates were 45.5% after a median of 4.0 months and 66.7% after a median of 10.0 months, for heart and kidney involvement, respectively. After a median follow-up of 20.5 months, two patients underwent successful autologous stem cell transplantation (ASCT), while another three patients were in preparation for ASCT. Three patients remained on daratumumab at the last follow-up. There were no unexpected toxicities and no grade III or IV adverse events, although more than half of our patients were in stage IIIa or IIIb. CONCLUSION: Daratumumab proved to be highly effective in newly diagnosed AL amyloidosis with excellent hematologic and organ response rates, a remarkable safety profile, and good tolerability even in patients with advanced stage of disease.

Gut microbiota, nutrient sensing and energy balance.

The gastrointestinal (GI) tract is a highly specialized sensory organ that provides crucial negative feedback during a meal, partly via a gut-brain axis. More specifically, enteroendocrine cells located throughout the GI tract are able to sense and respond to specific nutrients, releasing gut peptides that act in a paracrine, autocrine or endocrine fashion to regulate energy balance, thus controlling both food intake and possibly energy expenditure. Furthermore, the gut microbiota has been shown to provide a substantial metabolic and physiological contribution to the host, and metabolic disease such as obesity has been associated with aberrant gut microbiota and microbiome. Interestingly, recent evidence suggests that the gut microbiota can impact the gut-brain axis controlling energy balance, at both the level of intestinal nutrient-sensing mechanisms, as well as potentially at the sites of integration in the central nervous system. A better understanding of the intricate relationship between the gut microbiota and host energy-regulating pathways is crucial for uncovering the mechanisms responsible for the development of metabolic diseases and for possible therapeutic strategies.

Impact of high-fat feeding on basic helix-loop-helix transcription factors controlling enteroendocrine cell differentiation.

BACKGROUND AND OBJECTIVES: Gut hormones secreted by enteroendocrine cells (EECs) play a major role in energy regulation. Differentiation of EEC is controlled by the expression of basic helix-loop-helix (bHLH) transcription factors. High-fat (HF) feeding alters gut hormone levels; however, the impact of HF feeding on bHLH transcription factors in mediating EEC differentiation and subsequent gut hormone secretion and expression is not known. METHODS: Outbred Sprague-Dawley rats were maintained on chow or HF diet for 12 weeks. Gene and protein expression of intestinal bHLH transcription factors, combined with immunofluorescence studies, were analyzed for both groups in the small intestine and colon. Gut permeability, intestinal lipid and carbohydrate transporters as well as circulating levels and intestinal protein expression of gut peptides were determined. RESULTS: We showed that HF feeding resulted in hyperphagia and increased adiposity. HF-fed animals exhibited decreased expression of bHLH transcription factors controlling EEC differentiation (MATH1, NGN3, NEUROD1) and increased expression of bHLH factors modulating enterocyte expression. Furthermore, HF-fed animals had decreased number of total EECs and L-cells. This was accompanied by increased gut permeability and expression of lipid and carbohydrate transporters, and a decrease in circulating and intestinal gut hormone levels. CONCLUSIONS: Taken together, our results demonstrate that HF feeding caused decreased secretory lineage (that is, EECs) differentiation through downregulation of bHLH transcription factors, resulting in reduced EEC number and gut hormone levels. Thus, impaired EEC differentiation pathways by HF feeding may promote hyperphagia and subsequent obesity.

Decreased intestinal nutrient response in diet-induced obese rats: role of gut peptides and nutrient receptors.

BACKGROUND AND AIMS: Diet-induced obesity (DIO) is an excellent model for examining human obesity comprising both genotypic and environmental (diet) factors. Decreased responsiveness to peripheral satiety signaling may be responsible for the hyperphagia in this model. In this study, we investigated responses to nutrient-induced satiation in outbred DIO and DIO-resistant (DR) rats fed a high-energy/high-fat (HE/HF) diet as well as intestinal satiety peptide content, intestinal nutrient-responsive receptor abundance and vagal anorectic receptor expression. METHODS: Outbred DIO and DR rats fed a HE/HF diet were tested for short-term feeding responses following nutrient (glucose and intralipid (IL)) gastric loads. Gene and protein expressions of intestinal satiety peptides and fatty acid-responsive receptors were examined from isolated proximal intestinal epithelial cells and cholecystokinin-1 receptor (CCK-1R) and leptin receptor (LepR) mRNA from the nodose ganglia of DIO and DR animals. RESULTS: DIO rats were less responsive to IL- (P<0.05) but not glucose-induced suppression of food intake compared with DR rats. DIO rats exhibited decreased CCK, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1; P<0.05 for each) protein expression compared with DR rats. Also, DIO rats expressed more G-protein-coupled receptor 40 (GPR40; P<0.0001), GPR41 (P<0.001) and GPR120 (P<0.01) relative to DR rats. Finally, there were no differences in mRNA expression for CCK-1R and LepR in the nodose ganglia of DIO and DR rats. CONCLUSIONS: Development of DIO may be partly due to decreased fat-induced satiation through low levels of endogenous satiety peptides, and changes in intestinal nutrient receptors.

Current and emerging concepts on the role of peripheral signals in the control of food intake and development of obesity.

The gastrointestinal peptides are classically known as short-term signals, primarily inducing satiation and/or satiety. However, accumulating evidence has broadened this view, and their role in long-term energy homeostasis and the development of obesity has been increasingly recognised. In the present review, the recent research involving the role of satiation signals, especially ghrelin, cholecystokinin, glucagon-like peptide 1 and peptide YY, in the development and treatment of obesity will be discussed. Their activity, interactions and release profile vary constantly with changes in dietary and energy influences, intestinal luminal environment, body weight and metabolic status. Manipulation of gut peptides and nutrient sensors in the oral and postoral compartments through diet and/or changes in gut microflora or using multi-hormone 'cocktail' therapy are among promising approaches aimed at reducing excess food consumption and body-weight gain.

Up-regulation of intestinal type 1 taste receptor 3 and sodium glucose luminal transporter-1 expression and increased sucrose intake in mice lacking gut microbiota.

The chemosensory components shared by both lingual and intestinal epithelium play a critical role in food consumption and the regulation of intestinal functions. In addition to nutrient signals, other luminal contents, including micro-organisms, are important in signalling across the gastrointestinal mucosa and initiating changes in digestive functions. A potential role of gut microbiota in influencing food intake, energy homeostasis and weight gain has been suggested. However, whether gut microbiota modulates the expression of nutrient-responsive receptors and transporters, leading to altered food consumption, is unknown. Thus, we examined the preference for nutritive (sucrose) and non-nutritive (saccharin) sweet solutions in germ-free (GF, C57BL/6J) mice compared with conventional (CV, C57BL/6J) control mice using a two-bottle preference test. Then, we quantified mRNA and protein expression of the sweet signalling protein type 1 taste receptor 3 (T1R3) and α-gustducin and Na glucose luminal transporter-1 (SGLT-1) of the intestinal epithelium of both CV and GF mice. Additionally, we measured gene expression of T1R2, T1R3 and α-gustducin in the lingual epithelium. We found that, while the preference for sucrose was similar between the groups, GF mice consumed more of the high concentration (8 %) of sucrose solution than CV mice. There was no difference in either the intake of or the preference for saccharin. GF mice expressed significantly more T1R3 and SGLT-1 mRNA and protein in the intestinal epithelium compared with CV mice; however, lingual taste receptor mRNA expression was similar between the groups. We conclude that the absence of intestinal microbiota alters the expression of sweet taste receptors and GLUT in the proximal small intestine, which is associated with increased consumption of nutritive sweet solutions.

Differential feeding behavior and neuronal responses to CCK in obesity-prone and -resistant rats.

Deficits in satiation signals are strongly suspected of accompanying obesity and contributing to its pathogenesis in both humans and rats. One such satiation signal is cholecystokinin (CCK), whose effects on food intake are diminished in animals adapted to a high fat diet. In this study, we tested the hypothesis that diet-induced obese prone (OP) rats exhibit altered feeding and vagal responses to systemic (IP) administration of CCK-8 compared to diet-induced obese resistant (OR) rats. We found that CCK (4.0 microg/kg) suppressed food intake significantly more in OP than OR rats. To determine whether enhanced suppression of feeding is accompanied by altered vagal sensory responsiveness, we examined dorsal hindbrain expression of Fos-like immunoreactivity (Fos-Li) following IP CCK injection in OP and OR rats. After 4.0 microg/kg CCK, there were significantly more Fos-positive nuclei in the NTS of OP compared to OR rats. Treatment with 8.0 microg/kg CCK resulted in no significant difference in food intake or in Fos-Li between OP and OR rats. Also, we found that OP rats were hyperphagic on a regular chow diet and gained more weight compared to OR rats. Finally OP rats had decreased relative fat pad mass compared to OR rats. Collectively, these results show that OP rats exhibit a different behavioral and vagal neuronal responses to CCK than OR rats.

Inflammatory bowel diseases are not associated with major hereditary conditions predisposing to thrombosis.

Patients with inflammatory bowel diseases (IBD) are at increased risk for thromboembolic complications. Our aim was to evaluate whether the increased risk for thrombosis in IBD could be due to a genetic association of IBD with hereditary prothrombotic conditions. In all, 102 IBD patients (51 with ulcerative colitis and 51 with Crohn's disease) with no history of thrombosis and 204 matched normal subjects were enrolled. DNA specimens were evaluated by PCR and restriction fragment length polymorphism for factor V Leiden, methylene tetrahydrofolate reductase (MTHFR) and prothrombin gene mutations. In IBD patients and matched controls the observed allele frequencies were similar, being 1.5% and 1.2% for factor V Leiden gene mutation, 1.1% and 0.7% for prothrombin gene mutation, and 45.1% and 47.4% for MTHFR gene mutation, respectively. These rates also were not significantly different when patients were analyzed according to age and sex distribution, diagnosis, and extension and clinical type of disease. In conclusion, our study shows no association between IBD and the most frequent hereditary prothrombotic conditions. Other factors should be evaluated in order to understand the mechanisms underlying the thrombotic risk of IBD.

The G1691 --> A mutation of factor V, but not the G20210 --> A mutation of factor II or the C677 --> T mutation of methylenetetrahydrofolate reductase genes, is associated with venous thrombosis in patients with lupus anticoagulants.

Arterial and venous thrombosis are the most common manifestations of antiphospholipid syndrome. To investigate whether genetic determinants contribute to their thrombotic risk, we studied the prevalence of the G1691 --> A mutation in the gene coding for factor V, the G20210 --> A mutation in the prothrombin gene and the C677 --> T mutation in the methylenetetrahydrofolate reductase gene in 152 patients with lupus anticoagulants. One hundred and twenty-eight cases (84%) also had increased titres of anticardiolipin antibodies. History of thrombosis was present in 96 patients (63%); 67 suffered from venous thrombosis only, 23 cases had arterial thrombosis only, six patients had both venous and arterial thrombosis. Five patients were heterozygous for the G1691 --> A mutation in the factor V gene (3%). All of them (100%) suffered from venous thrombosis compared with 68 out of the 147 cases without the mutation (46%) (P = 0.0474). The prevalence of the G20210 --> A mutation in the prothrombin gene was evaluated in 145 patients; eight of these patients were heterozygous (5%). Four of these patients (50%) experienced venous thrombosis compared with 65 out of the 137 patients without the mutation (47%) (P = ns). Neither mutation was associated with arterial thrombotic events. No patient carried both mutations. The C677 --> T mutation in the methylenetetrahydrofolate reductase gene was assessed in 83 patients; 15 of them (18%) were homozygous and 37 (44%) were heterozygous. There was no significant association between the status of the mutation and history of venous and arterial thrombosis. No significant correlation was found among the three groups. In conclusion, only the G1691 --> A mutation in the factor V gene was associated with the thrombotic risk of patients with lupus anticoagulants.

Apparently dominant transmission of a recessive disease: deficiency of factor VII in Iranian Jews.

In inherited disorders transmitted as autosomal recessive traits the children of affected individuals are usually asymptomatic and phenotypically normal because they are heterozygous for the defect. In an Iranian Jewish family with moderately severe deficiency of coagulation factor VII (an autosomal recessive bleeding disorder) the son of an affected woman was also affected. DNA analysis of the factor VII gene showed that this unusual situation was due to the fact that he inherited an abnormal allele with the Ala244Val missense mutation from both the homozygous mother and the heterozygous father. The parents, although not overtly consanguineous, belong to the same ethnic group of Iranian Jews, among whom this factor VII gene mutation reaches high frequencies (between 2 and 3%) in the heterozygous state.

Prothrombotic genetic risk factors in young survivors of myocardial infarction.

It has long been thought that an individual thrombotic tendency increases the risk of myocardial infarction, especially in young adults. Several "prothrombotic" genetic factors that may influence the individual thrombotic risk have been identified. To investigate the association between the risk of myocardial infarction at a young age and genetic factors thought to be associated with an increased tendency to thrombosis (the polymorphisms 4G/5G of the PAI-1 gene, PIA1/PIA2 of the platelet glycoprotein IIIa, C3550T of the platelet glycoprotein Ib gene, G10976A of the factor VII gene, C677T of the methylenetetrahydrofolate reductase gene, G1691A of the factor V gene, and G20210A of the prothrombin gene), we performed a case-control study evaluating 200 survivors (185 men, 15 women) of myocardial infarction who had experienced the event before the age of 45 years and 200 healthy subjects with a negative exercise test, individually matched for sex, age, and geographic origin with the cases. The presence of the PIA2 polymorphic allele was the only prothrombotic genetic factor associated with the risk of myocardial infarction at a young age. The odds ratio for carriers of the PIA2 allele compared with those of the PIA1 allele was 1.84 (95% confidence intervals (CI) 1.12 to 3.03). There was a significant interaction between the presence of the PIA2 allele and smoking: with their simultaneous presence, 46% (95% confidence intervals 11% to 81%) of premature myocardial infarctions were attributable to the interaction between the two factors. In conclusion, carrying the PIA2 polymorphic allele of platelet glycoprotein IIIa was the only genetic prothrombotic factor associated with the risk of developing myocardial infarction at a young age. The clinical expression of this genetic predisposition seems to be enhanced by smoking.

Congenital resistance to activated protein C in patients with lupus anticoagulants: evaluation of two functional assays.

The R506Q mutation ("Factor V Leiden") is responsible for the resistance to activated Protein C (aPCR), that is evaluated by coagulation tests. Such tests cannot be used in patients with lupus anticoagulants (LAs), due to the interfering effect exerted by these antibodies on "in vitro" phospholipid-dependent coagulation tests. For this reason, assays have been developed to evaluate aPCR that are insensitive to the presence of LA antibodies. We evaluated two such coagulation tests in the plasma of 82 consecutive patients with LAs. By polymerase chain reaction 3 patients (3.6%) were found heterozygous for the R506Q mutation. aPCR was evaluated by two clotting assays, proposed to be "insensitive" to the presence of LAs: 1. aPCR-tissue factor-based assay, using Factor V deficient plasma and 1:40 diluted test plasma; 2. aPCR-dRVVT-based assay with highly concentrated phospholipids. Their interassay coefficient of variation was 28% and 6.2%, respectively. Compared to the polymerase chain reaction analysis, the 2 tests displayed the following characteristics: sensitivity 67% vs 100%, specificity 92% vs 96%, positive predictive value 25% vs 50%, negative predictive value 99% vs 100%. respectively. Among LA patients without the R506Q mutation, 5 scored positive in the aPCR-tissue factor-based assay, 2 in the aPCR-dRVVT-based assay and another one in both assays. Our findings suggest that the aPCR-dRVVT-based test is more reliable and sensitive than the aPCR-tissue factor-based one to the R506Q mutation in patients with LAs. Both assays, when negative, make unlikely the presence of the R506Q mutation. Polymerase chain reaction analysis remains, however, to be performed when either test is positive.

High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives.

BACKGROUND: Idiopathic cerebral-vein thrombosis can cause serious neurologic disability. We evaluated risk factors for this disorder, including genetic risk factors (mutations in the genes encoding factor V and prothrombin) and nongenetic risk factors (such as the use of oral contraceptive agents). We compared the prevalence of these risk factors in 40 patients with cerebral-vein thrombosis, 80 patients with deep-vein thrombosis of the lower extremities, and 120 healthy controls. The G1691A mutation in the factor V gene and the G20210A prothrombin-gene mutation, which are established genetic risk factors for venous thrombosis, were studied. We also assessed the use of oral contraceptives and other risk factors for thrombosis. RESULTS: The prevalence of the prothrombin-gene mutation was higher in patients with cerebral-vein thrombosis (20 percent) than in healthy controls (3 percent; odds ratio, 10.2; 95 percent confidence interval, 2.3 to 31.0) and was similar to that in patients with deep-vein thrombosis (18 percent). Similar results were obtained for the mutation in the factor V gene. The use of oral contraceptives was more frequent among women with cerebral-vein thrombosis (96 percent) than among controls (32 percent; odds ratio, 22.1; 95 percent confidence interval, 5.9 to 84.2) and among those with deep-vein thrombosis (61 percent; odds ratio, 4.4; 95 percent confidence interval, 1.1 to 17.8). For women who were taking oral contraceptives and who also had the prothrombin-gene mutation (seven patients with cerebral-vein thrombosis but only one control), the odds ratio for cerebral-vein thrombosis rose to 149.3 (95 percent confidence interval, 31.0 to 711.0). CONCLUSIONS: Mutations in the prothrombin gene and the factor V gene are associated with cerebral-vein thrombosis. The use of oral contraceptives is also strongly and independently associated with the disorder. The presence of both the prothrombin-gene mutation and oral-contraceptive use raises the risk of cerebral-vein thrombosis further.

PIP: The role of the prothrombin-gene mutation in idiopathic cerebral-vein thrombosis and its interaction with other risk factors was investigated in a study of 40 patients (9 men and 31 women) 15-64 years of age who presented to a thrombosis center in Milan, Italy, in 1991-97 after a first episode of this thrombosis. Also enrolled were 80 men and women randomly selected from patients screened at the same center during the study period after a first documented episode of proximal deep-vein thrombosis of the lower extremities. 120 healthy controls were matched to cerebral-vein thrombosis patients by sex, age, geographic origin, and education. 20% of patients with cerebral-vein thrombosis (odds ratio (OR), 10.2; 95% confidence interval (CI), 2.3-31.0), 18% of those with deep-vein thrombosis, and 3% of controls were carriers of the prothrombin-gene mutation. Factor V mutation was more prevalent in patients with cerebral-vein thrombosis (15%) than controls (3%) (OR, 7.8; 95% CI, 1.8-34.1), but the thrombotic risks associated with these two mutations were independent of each other. Oral contraceptive (OC) ever-use was more frequent among women with cerebral-vein thrombosis (96%) (OR, 22.1; 95% CI, 5.9-84.2) and deep-vein thrombosis (61%) (OR, 4.4; 95% CI, 1.1-17.8) compared with controls (32%). For the 7 women with cerebral-vein thrombosis who were both OC ever-users and had the prothrombin-gene mutation, the thrombotic risk rose to 149.3 (95% CI, 31.0-711.0). These findings show that there is a hypercoagulable state in 35% of patients with idiopathic cerebral-vein thrombosis. Although screening for the prothrombin-gene mutation in young women before they are prescribed OCs is unlikely to be cost-effective, carriers of the mutation who have had a thrombosis episode should discontinue OC use.