Does prophylactic subcutaneous heparin increase the risk of wound infection after colorectal surgery?

Chemical prophylaxis using unfractionated heparin (UH) and low-molecular weight heparin is used in surgical patients to prevent venous thromboembolism. There is some evidence that prophylactic doses of heparin may increase the rate of surgical site infection (SSI) after elective orthopedic procedures. Little is known regarding the effect of heparin on SSI after colorectal procedures. We performed this study to study the effect of prophylactic unfractionated heparin on the rate of SSI after colorectal procedures. We did a retrospective analysis of 155 consecutive cases of patients of a single colorectal surgeon who underwent colorectal resection. Subcutaneous unfractionated heparin was given to 52 patients (29%). The rate of SSI in the group that received UH was 33 per cent versus 28 per cent in the group that did not receive UH (P = 0.31). There was also no significant effect of prophylactic heparin on SSI noted among any patient subgroup. The use of prophylactic unfractionated heparin after colorectal procedures does not seem to increase the rate of surgical site infection.     

Appropriateness of direct oral anticoagulant dosing and its relation to drug levels in atrial fibrillation patients

Journal of Thrombosis and Thrombolysis - Direct oral anticoagulants (DOACs) are commonly administered at a level that is lower than that recommended by dose reduction criteria. This raises concern...     

Taxing working memory with syntax: bihemispheric modulations

Motivated by claims that relegate the syntactic functions of Broca's region to working memory (WM) and not to language‐specific mechanisms, we conducted an fMRI and an aphasia study that featured two varieties of intrasentential dependency relations: One was syntactic movement (e.g., Which boy does the girl think ? examined Steven?), the other was antecedent–reflexive binding (e.g., Jill thinks the boy examined himself). In both, WM is required to link two nonadjacent positions. Syntactically, they are governed by distinct rule systems. In health, the two dependencies modulated activity in distinct brain regions within the left inferior frontal gyrus and the left middle temporal gyrus. Binding uniquely modulated activation in the right frontal lobe. Receptive abilities in brain damaged patients likewise distinguished among these syntactic types. The results indicate that sentence comprehension is governed by syntactically carved neural chunks and provide hints regarding a language related region in the right hemisphere. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.     

Identification of nif genes in N2-fixing bacterial strains isolated from rice fields along the Yangtze River Plain

The aim of this research was to identify nifH and nifHDKYE ' genes in twenty strains of N2-fixing heterotrophic bacteria isolated from rice fields in the Yangtze River Plain. Southern hybridization of the total DNA from each strain was performed with the Klebsiella pneumoniae nifHDKYE ' gene probe (6.2 kb Eco RI fragment from pSA30) and the Azospirillum brasilense nifH gene probe (0.6 kb Eco RI-Hin dIII fragment from pHU8). We found that Eco RI fragments of total DNA from Aeromonas hydrophila HY2, Bacillus azotoformans FD, Bacillus licheniformis NCH1, NCH5, WH4, Bacillus brevis NC2, Bacillus pumilus NC12, Bacillus cereus NCH2, Citrobacter freundii HY5, HY9, Derxia gummosa HZ5, Pseudomonas mendocina HZ1 and Pseudomonas pseudoalcaligenes WH3 were positively hybridized with both of the probes. Agrobacterium radiobacter HY17, Corynebacterium sp. HY12, YZ and Pseudomonas sp. HY11 had Eco RI fragments hybridized with the K. pneumoniae nifHDKYE ' gene probe. An Eco RI fragment of total DNA from Bacillus megaterium YY4 was positively hybridized to the A. brasilense nifH gene probe. No hybridization sign was found in the total DNA fragments from Alcaligenes cupidus YY6 and Corynebacterium sp. NC11 hybridized with either of the gene probes. The data provide the number and size of EcoRI fragments of the total DNA hybridized with the nif gene probes for these strains of rarely studied species, suggesting additional evidence for N2 fixing and nif gene diversity of N2-fixing bacteria in rice fields along the Yangtze River Plain.     

Behavioral, electrophysiological, and histopathological characterization of a severe murine chronic demyelinating polyneuritis model

The objective of this study was to define the behavioral, electrophysiological, and morphological characteristics of spontaneous autoimmune peripheral polyneuropathy (SAPP) in female B7-2 deficient non-obese diabetic (NOD) mice. A cohort of 77 female B7-2 deficient and 31 wild-type control NOD mice were studied from 18 to 40 weeks of age. At pre-defined time points, the dorsal caudal tail and sciatic motor nerve conduction studies (MNCS) were performed. Sciatic nerves were harvested for morphological evaluation. SAPP mice showed slowly progressive severe weakness in hind and forelimbs without significant recovery after 30 weeks of age. MNCS showed progressive reduction in mean compound motor action potential amplitudes and conduction velocities, and increase in mean total waveform duration from 24 to 27 weeks of age, peaking between 32 and 35 weeks of age. Toluidine blue-stained, semi-thin plastic-embedded sections demonstrated focal demyelination associated with mononuclear cell infiltration early in the disease course, with progressively diffuse demyelination and axonal loss associated with more intense mononuclear infiltration at peak severity. Immunohistochemistry confirmed macrophage-predominant inflammation. This study verifies SAPP as a progressive, unremitting chronic inflammatory demyelinating polyneuropathy with axonal loss.     

Malfunctioning DNA Damage Response (DDR) Leads to the Degeneration of Nigro-Striatal Pathway in Mouse Brain

Pronounced neuropathology is a feature of ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS), which are both genomic instability syndromes. The Nbs1 protein, which is defective in NBS, is a component of the Mre11/RAD50/NBS1 (MRN) complex. This complex plays a major role in the early phase of the cellular response to double strand breaks (DSBs) in the DNA. Among others, MRN is required for timely activation of the protein kinase ATM (A-T mutated), which is disrupted in patients with A-T. Earlier reports show that Atm-deficient mice exhibit severe degeneration of tyrosine hydroxylase (TH)-positive dopaminergic nigro-striatal neurons and their terminals in the striatum. This cell loss is accompanied by a large reduction in immunoreactivity for the dopamine transporter protein (DAT) in the striatum. To test whether Nbs1 inactivation also affects the integrity of the nigro-striatal pathway, we examined this pathway in a murine model with conditional inactivation of the Nbs1 gene in central nervous system (Nbs1-CNS-Δ). We report that this model has a reduction in TH-positive cells in the substantia nigra. This phenomenon was seen at very early age, while Atm−/− mice showed a progressive age-dependent reduction. Furthermore, we observed an age-dependent increase in the level of TH in the striatum of Atm−/− and Nbs1-CNS-Δ mice. In addition to the altered expression of TH, we also found a reduction of DAT in the striatum of both Atm−/− and Nbs1-CNS-Δ mice at 60 days of age. Finally, microglial recruitment and alterations in the levels of various neurotrophic factors were also observed. These results indicate that malfunctioning DNA damage response severely affects the integrity of the nigro-striatal pathway and suggest a new neurodegenerative pathway in Parkinsonian syndromes.     

A Role for Vascular Deficiency in Retinal Pathology in a Mouse Model of Ataxia-Telangiectasia

Ataxia-telangiectasia is a multifaceted syndrome caused by null mutations in the ATM gene, which encodes the protein kinase ATM, a key participant in the DNA damage response. Retinal neurons are highly susceptible to DNA damage because they are terminally differentiated and have the highest metabolic activity in the central nervous system. In this study, we characterized the retina in young and aged Atm-deficient mice (Atm^−/−). At 2 months of age, angiography revealed faint retinal vasculature in Atm^−/− animals relative to wild-type controls. This finding was accompanied by increased expression of vascular endothelial growth factor protein and mRNA. Fibrinogen, generally absent from wild-type retinal tissue, was evident in Atm^−/− retinas, whereas mRNA of the tight junction protein occludin was significantly decreased. Immunohistochemistry labeling for occludin in 6-month-old mice showed that this decrease persists in advanced stages of the disease. Concurrently, we noticed vascular leakage in Atm^−/− retinas. Labeling for glial fibrillary acidic protein demonstrated morphological alterations in glial cells in Atm^−/− retinas. Electroretinographic examination revealed amplitude aberrations in 2-month-old Atm^−/− mice, which progressed to significant functional deficits in the older mice. These results suggest that impaired vascularization and astrocyte–endothelial cell interactions in the central nervous system play an important role in the etiology of ataxia-telangiectasia and that vascular abnormalities may underlie or aggravate neurodegeneration.Some brain disorders may have a vascular origin,^1,2 and vascular diseases can be directly linked to neuronal and synaptic dysfunction through changes in the blood flow, increase in blood–brain barrier permeability, and in nutrient supply.³ A healthy brain relies on the proper function and communication of all cells comprising the neurovascular unit: neurons, astrocytes, brain endothelium, and vascular smooth muscle cells.⁴Impaired genomic stability interferes with cellular homeostasis and poses a constant threat to cellular viability.⁵ The cell combats this threat by activating the DNA damage response (DDR), a complex signaling network that detects the DNA lesions, promotes their repair, and temporarily modulates cellular metabolism while the damage is being repaired.⁶ The DDR is vigorously activated by DNA double-strand breaks (DSBs), a particularly cytotoxic DNA lesion induced by ionizing radiation, radiomimetic chemicals, and oxygen radicals.^7,8 The DNA damage response is a hierarchical process executed by sensor/mediator proteins that accumulate at DSB sites and by protein kinases that serve as transducers of the DNA damage alarm to numerous downstream effectors.⁶ The primary transducer of the cellular response to DSBs is the protein kinase ATM, which phosphorylates many key players in the various branches of the DDR.⁹Ataxia-telangiectasia (A-T) is an autosomal recessive disorder caused by mutations in the ATM gene that encodes the ATM protein.¹⁰ A-T is characterized by progressive neurodegeneration affecting mainly the cerebellum, which develops into severe neuromotor dysfunction; peripheral neuropathy; immunodeficiency that spans the B- and T-cell systems; thymic and gonadal atrophy; marked predisposition to lymphoreticular malignancies; and chromosomal fragility and acute sensitivity to ionizing radiation. Cultured ATM-deficient cells exhibit severe cellular sensitivity to DSB-inducing agents, with markedly defective DSB response.DSBs are constantly induced in all body cells by metabolic byproducts such as oxygen radicals. Oxidative stress has been consistently associated with various neurodegenerative conditions.^11–14 Indeed, there is substantial evidence for a role of oxidative damage in the progression of neurodegenerative disorders, including Parkinson''s and Alzheimer''s diseases.¹⁵ Similarly, elevated oxidative stress has been identified in several DNA repair deficiencies, including A-T.^16–22 Notably, ATM has recently been shown to be activated by oxidative stress.²³ Ocular tissues, especially the retina, are exposed to extremely high levels of reactive oxygen species. Nevertheless, retinal neurodegeneration has not been reported in A-T patients. The ocular manifestation of the disease reported to date is scleral telangiectasia^24,25 and saccadic abnormalities.²⁶ Moreover, no retinal pathology has been described to date in Atm-deficient mice despite their increased sensitivity to reactive oxygen species–inducing agents.²⁷ We examined the link between retinal vascular pathology and function in young and aging Atm-deficient mice. We present evidence for vascular changes that accompany neuronal deficiencies in the retina.