The crystal structure of ampicillin trihydrate {systematic name: 6‐d(−)‐α‐aminophenylacetamidopenicillanic acid trihydrate}, C16H19N3O4S·3H2O, a broad‐spectrum β‐lactam antibiotic of the ...aminopenicillin type, has been determined from synchrotron X‐ray powder diffraction data. The three water molecules form an infinite hydrogen‐bonded chain through the crystal structure, with hydrogen bonds to the NH3+, COO−, C=O and NH groups of the ampicillin molecules.
In the article (BMJ 2017;359, doi: 10.1136/bmj.j5058 ), instances of "rivaroxaban 20 mg twice daily" should read as "rivaroxaban 20 mg once daily" and "edoxaban 60 mg twice daily" as "edoxaban 60 mg ...once."
Helicobacter pylori is the causative organism of peptic ulcer disease and has two putative virulence determinants: the cagA gene which encodes a protein of unknown function in 60% of strains, and the ...vacA gene, which is present in all strains, although active cytotoxin is produced in only about 50% of these. The relationship between genotypes of both cagA and vacA and resultant gastroduodenal pathology is unclear. The objective of this study was to correlate vacA genotype and cagA status with gastroduodenal pathology.
One hundred and six dyspeptic patients were studied (average age 56 years, range 19-86 years, 56 men) referred for routine endoscopy. Macroscopic evidence of gastroduodenal disease was noted and antral biopsies taken for culture and genotyping of H. pylori. The polymerase chain reaction (PCR) was used to detect the cagA and vacA genes of H. pylori using specific primers.
Seventy eight of the 106 (73.6%) patients were cagA positive. Of those who had peptic ulcer disease 29/32 (90.6%) were cagA positive. The presence of the cagA gene was significantly associated with peptic ulcer disease (P = 0.006). The presence of the vacA s1 genotype was also significantly associated with peptic ulcer disease (P = 0.01). The presence of the cagA gene was significantly associated with the vacA s1 genotype (P < 0.001). There was no significant difference in the distribution of the s1/m1 and s1/m2 strains between ulcer and non-ulcer patients.
There is a significant association of the cagA gene and vacA s1 signal sequence with gastroduodenal ulcer disease. The relationship of the various other vacA genotypes to gastroduodenal ulcer disease is less clear.
Any plant not sown from seed is often labeled a weed in improved pastures of New Zealand. Most improved pastures are a mix of perennial ryegrass and white clover but generally are infested with ...broadleaf weeds. Changes in forage production due to individual weeds were determined using measurements of perennial ryegrass and white clover before and after dairy cattle, beef cattle, or sheep grazing under, near, and far from individual plants of six rosette-forming weed species throughout a growing season. The larger weeds, bull thistle and musk thistle, reduced the amount of forage utilized 42 and 72%, respectively, in beef cattle- and sheep-grazed hill-country pastures. Forage production under and near Canada thistle, hedge mustard, broadleaf plantain, and hairy buttercup in a dairy pasture was greater (136, 140, 178, and 450%, respectively) than in the control areas. Although the dairy pasture was grazed following recommended grazing procedures, our results indicate that this grazing system was not maximizing forage yield potentials of perennial ryegrass and white clover and that these weeds served as an indicator that the pasture was being overgrazed.
The two lowest-lying states (
X
̃
2
A′′ and
A
̃
2
A′) of the hydroxyethynyl radical (CCOH), an isomer of the ketenyl radical (HCCO), have been investigated theoretically using ab initio electronic ...structure theory. The ground and first excited electronic states of CCOH were determined to have
trans-planar bent structures. At the TZ3P(2f,2d) CCSD(T) level of theory the two lowest-lying states of CCOH were predicted to lie 54.2 kcal/mol (2.35 eV, 19000 cm
−1) and 65.8 kcal/mol (2.85 eV, 23000 cm
−1) classically above the ground state of HCCO. Due to its large dipole moments and significantly large vibrational infrared (IR) intensities, the CCOH radical may be suitable for microwave and IR spectroscopic investigations.
The exon-junction complex (EJC) performs essential RNA processing tasks
1
-
5
. Here, we describe the first human disorder, Thrombocytopenia with Absent Radii
6
(TAR), caused by deficiency in one of ...the four EJC subunits. A compound inheritance mechanism of a rare null allele and one of two low-frequency SNPs in the regulatory regions of
RBM8A,
encoding the Y14 subunit of EJC, causes TAR. We found that this mechanism explained 53 of 55 cases (P<5×10
−228
) with the rare congenital malformation syndrome. Fifty-one of those 53 carried a previously associated
7
submicroscopic deletion of 1q21.1; two carried a truncation or frameshift null mutation in
RBM8A
. We show that the two regulatory SNPs result in reduction of
RBM8A
transcription
in vitro
and that Y14 expression is reduced in platelets from TAR cases. Our data implicate Y14 insufficiency, and presumably EJC defect, as the cause of TAR syndrome.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary Background Carriers of a germline TP53 pathogenic variant have a substantial lifetime risk of developing cancer. In 2011, we did a prospective observational study of members of families who ...chose to either undergo a comprehensive surveillance protocol for individuals with Li-Fraumeni syndrome or not. We sought to update our assessment of and modify the surveillance protocol, so in this study we report both longer follow-up of these patients and additional patients who underwent surveillance, as well as update the originally presented surveillance protocol. Methods A clinical surveillance protocol using physical examination and frequent biochemical and imaging studies (consisting of whole-body MRI, brain MRI, breast MRI, mammography, abdominal and pelvic ultrasound, and colonoscopy) was introduced at three tertiary care centres in Canada and the USA on Jan 1, 2004, for carriers of TP53 pathogenic variants. After confirmation of TP53 mutation, participants either chose to undergo surveillance or chose not to undergo surveillance. Patients could cross over between groups at any time. The primary outcome measure was detection of asymptomatic tumours by surveillance investigations. The secondary outcome measure was 5 year overall survival established from a tumour diagnosed symptomatically (in the non-surveillance group) versus one diagnosed by surveillance. We completed survival analyses using an as-treated approach. Findings Between Jan 1, 2004, and July 1, 2015, we identified 89 carriers of TP53 pathogenic variants in 39 unrelated families, of whom 40 (45%) agreed to surveillance and 49 (55%) declined surveillance. 19 (21%) patients crossed over from the non-surveillance to the surveillance group, giving a total of 59 (66%) individuals undergoing surveillance for a median of 32 months (IQR 12–87). 40 asymptomatic tumours have been detected in 19 (32%) of 59 patients who underwent surveillance. Two additional cancers were diagnosed between surveillance assessments (false negatives) and two biopsied lesions were non-neoplastic entities on pathological review (false positives). Among the 49 individuals who initially declined surveillance, 61 symptomatic tumours were diagnosed in 43 (88%) patients. 21 (49%) of the 43 individuals not on surveillance who developed cancer were alive compared with 16 (84%) of the 19 individuals undergoing surveillance who developed cancer (p=0·012) after a median follow-up of 46 months (IQR 22–72) for those not on surveillance and 38 months (12–86) for those on surveillance. 5 year overall survival was 88·8% (95% CI 78·7–100) in the surveillance group and 59·6% (47·2–75·2) in the non-surveillance group (p=0·0132). Interpretation Our findings show that long-term compliance with a comprehensive surveillance protocol for early tumour detection in individuals with pathogenic TP53 variants is feasible and that early tumour detection through surveillance is associated with improved long-term survival. Incorporation of this approach into clinical management of these patients should be considered. Funding Canadian Institutes for Heath Research, Canadian Cancer Society, Terry Fox Research Institute, SickKids Foundation, and Soccer for Hope Foundation.
Epilepsy is defined by the seemingly random occurrence of spontaneous seizures. The ability to anticipate seizures would enable preventative treatment strategies. A central but unresolved question ...concerns the relationship of seizure timing to fluctuating rates of interictal epileptiform discharges (here termed interictal epileptiform activity, IEA), a marker of brain irritability observed between seizures by electroencephalography (EEG). Here, in 37 subjects with an implanted brain stimulation device that detects IEA and seizures over years, we find that IEA oscillates with circadian and subject-specific multidien (multi-day) periods. Multidien periodicities, most commonly 20-30 days in duration, are robust and relatively stable for up to 10 years in men and women. We show that seizures occur preferentially during the rising phase of multidien IEA rhythms. Combining phase information from circadian and multidien IEA rhythms provides a novel biomarker for determining relative seizure risk with a large effect size in most subjects.
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