Miracle-dz/UniFAR-FTUs huggingface dataset:
The Significance of Protein Binding of Penicillins

A large volume of data on variations in serum penicillin levels has been obtained from work carried out with depot preparations of procaine benzyl penicillin in oil (to be published). Figure 1 shows frequency histograms of blood levels obtained in humans 24 hours after a single fixed dose of the same preparation. Large groups of individuals were involved and there was an interesting difference between Clinic C and the other two clinics. With a preparation of this type there is the added variable of the rate of release of penicillin from the oil depot into the blood stream. In choosing the dose of a penicillin for therapy presumably it should be onse which is adequate even for individuals with the lowest serum levels found in this type of distribution. Usually only mean blood levels are quoted and no idea is given of the range found in a normal population, and no comparison appears to have been made of the ranges of the various penicillins. A penicillin producing a small range of blood levels at any given time would be advantageous.
Primary and revision total hip arthroplasty for patients 90 years of age and older.

OBJECTIVE To assess the reliability, durability, and safety of primary and revision total hip arthroplasty (THA) in patients 90 years of age and older. PATIENTS AND METHODS Between 1970 and 1997, 66 THAs, 48 primary and 18 revision, were done for 65 patients aged 90 to 104 years (mean, 92 years). The Harris hip score was used to assess hip pain and function. RESULTS Patients were evaluated for pain, function, and satisfaction at a mean of 3.2 years after the THA. The Harris hip scores improved significantly (P = .004) for both primary and revision groups: from preoperative mean scores of 39 and 45 points to follow-up scores of 80 and 75 points, respectively. Two patients died in the early postoperative period of causes related to the operation. Thirty-seven other patients were dead at last follow-up and had lived a mean +/- SD of 6 +/- 2.2 years after the primary THA and 4.2 +/- 2.8 years after the revision THA. No hips required subsequent revision. CONCLUSION Total hip replacement was reliable, durable, and safe in this study group. Primary care physicians and surgeons should be aware that both primary and revision total hip replacement can be done safely and effectively in patients aged 90 years and older and can result in years of relief of pain and functional improvement.
Update on dual antiplatelet therapy for percutaneous coronary intervention

Platelet activation is central in the vascular response to percutaneous coronary intervention (PCI). In addition, patients with coronary artery disease (CAD), particularly those with an acute coronary syndrome (ACS), have pre-existing platelet hyper-reactivity. Together, these are among the factors that predispose to stent thrombosis (ST). Thus, dual antiplatelet therapy (DAT), which consists of aspirin and a thienopyridine, forms the cornerstone of pharmacotherapy following PCI with the goal of reducing ST, as well as ischaemic events related to the underlying CAD. Adherence to DAT, and the need for a longer duration of treatment, has become even more important for patients receiving drug-eluting stents (DES), as concerns have been raised regarding the increased risk of very late ST (>1 year) with the current generation of stents.1 Table 1 summarises the most recent guidelines on DAT following PCI which have been jointly published by the American College of Cardiology (ACC), American Heart Association (AHA) and Society for Cardiovascular Angiography and Interventions (SCAI). 2 3 Despite the routine use of clopidogrel, there is uncertainty about the optimal timing, dose and duration of thienopyridine therapy, and there is a lack of consensus on the management of patients requiring non-cardiac surgery or chronic anticoagulation while being treated with DAT. View this table: Table 1 ACC/AHA/SCAI recommendations for the use of antiplatelet agents in patients requiring PCI2 3 Although current practice in many parts of the world is to administer clopidogrel in the catheterisation laboratory at the time of ad hoc PCI, several clinical trials have evaluated the efficacy of pretreatment (table 2). 4–8 Overall, the data suggest a potential benefit of pretreatment with the 300 mg loading dose, though both PCI-CURE and PCI-CLARITY represent analyses in which the decision to perform PCI was made after randomisation to the two loading strategies. It appears that a 300 mg clopidogrel loading dose needs to be administered at least 6 h prior to …
Prevalence and Risk Factors for Hypertension in Hemophilia

Hypertension (HTN) is a major risk factor for intracranial hemorrhage. We, therefore, investigated the prevalence, treatment, and control of HTN in adult patients with hemophilia (PWH). PWH≥18 years (n=458) from 3 geographically different cohorts in the United States were evaluated retrospectively for HTN and risk factors. Results were compared with the nationally representative sample provided by the contemporary National Health and Nutrition Examination Survey (NHANES). PWH had a significantly higher prevalence of HTN compared with NHANES. Overall, the prevalence of HTN was 49.1% in PWH compared with 31.7% in NHANES. At ages 18 to 44, 45 to 64, 65 to 74, and ≥75 years, the prevalence of HTN for PWH was 31.8%, 72.6%, 89.7%, and 100.0% compared with 12.5%, 41.2%, 64.1%, and 71.7% in NHANES, respectively. Of treated hypertensive PWH, only 27.1% were controlled, compared with 47.7% in NHANES (all P<0.05). Age, body mass index, diabetes mellitus, and renal function were independently associated with HTN. Among patients with moderate or severe hemophilia there was a trend (≈1.5-fold) for higher odds of having HTN compared with patients with mild hemophilia. On the basis of these results, new care models for adult PWH and further studies for the causes of HTN in hemophilia are recommended.
Adrenal and ovarian autoimmunity.

Addison’s disease, described first by Thomas Addison (1), is quite rare and has been described in 40–110 cases per 1 000 000 inhabitants (2–4). Currently, in the developed countries the most common cause of primary adrenal failure is autoimmunity, causing up to 75–80% of the cases of adrenal insufficiency, while tuberculosis is the second most frequent cause, responsible for up to 15–20% of the cases. Many other rare causes are involved in 5–7% of patients (5, 6). Consequently, autoimmune Addison’s disease (AAD) can be considered as a synonym of the idiopathic form of adrenal failure. About 50–60% of AAD patients have or develop during their life other autoimmune disorders; in the remaining cases the adrenal failure manifests itself as an isolated disease (7). Four main types of polyglandular autoimmune disease (PGAD) have been classified by Neufeld & Blizzard (8) and AAD is a fundamental disease of PGAD types 1 and 2. AAD can present in three main clinical forms: (i) PGAD type 1, (ii) PGAD type 2, (iii) isolated (9–11).
Public Awareness of Melioidosis in Thailand and Potential Use of Video Clips as Educational Tools

Background Melioidosis causes more than 1,000 deaths in Thailand each year. Infection occurs via inoculation, ingestion or inhalation of the causative organism (Burkholderia pseuodmallei) present in soil and water. Here, we evaluated public awareness of melioidosis using a combination of population-based questionnaire, a public engagement campaign to obtain video clips made by the public, and viewpoints on these video clips as potential educational tools about the disease and its prevention. Methods A questionnaire was developed to evaluate public awareness of melioidosis, and knowledge about its prevention. From 1 March to 31 April 2012, the questionnaire was delivered to five randomly selected adults in each of 928 districts in Thailand. A video clip contest entitled “Melioidosis, an infectious disease that Thais must know” was run between May and October 2012. The best 12 video clips judged by a contest committee were shown to 71 people at risk from melioidosis (diabetics). Focus group interviews were used to evaluate their perceptions of the video clips. Results Of 4,203 Thais who completed our study questionnaire, 74% had never heard of melioidosis, and 19% had heard of the disease but had no further knowledge. Most participants in all focus group sessions felt that video clips were beneficial and could positively influence them to increase adherence to recommended preventive behaviours, including drinking boiled water and wearing protective gear if in contact with soil or environmental water. Participants suggested that video clips should be presented in the local dialect with simple words rather than medical terms, in a serious manner, with a doctor as the one presenting the facts, and having detailed pictures of each recommended prevention method. Conclusions In summary, public awareness of melioidosis in Thailand is very low, and video clips could serve as a useful medium to educate people and promote disease prevention. Presented in Part World Melioidosis Congress 2013, Bangkok, Thailand, 18–20 September 2013 (abstract OS VII-04).
German Inbound Investment, Corporate Tax Planning, and Thin Capitalization Rules - a Difference-in-Differences Approach

This paper investigates tax planning behavior by means of inter-company finance and the effectiveness of fighting back via thin-capitalization rules. A simple theoretical model, which considers the financing decision of a multinational company, is used to obtain empirical implications. The empirical analysis, based on German inbound investment data from 1996 until 2004, supports a significant impact of tax rate differences on the use of intra-company debt. The effectiveness of the German thin-capitalization rule is tested by using legal amendments as natural experiments. The results suggest that the German thin-capitalization rule induces significantly lower intra-firm debt-levels of inbound investments. Hence, tax planning via intra-firm finance is effectively limited.
Epidemiological review of Toxoplasma gondii infection in humans and animals in Portugal

SUMMARY Toxoplasmosis is a worldwide zoonosis. However, data from Portugal are limited and a considerable part of the literature is in Portuguese. Currently, the rate of congenital infection in Portugal is unknown, and almost nothing is known of sequelae of congenital toxoplasmosis. There is no recent general population-based serological survey of Toxoplasma gondii in humans in Portugal. In addition, there is little information on genetic characteristics of T. gondii in animals and humans. In the present paper, we review prevalence, clinical spectrum and epidemiology of T. gondii in humans and animals in Portugal. This knowledge should be useful to biologists, public health workers, physicians and veterinarians.
t(11;18)(q21;q21) of mucosa‐associated lymphoid tissue lymphoma results from illegitimate non‐homologous end joining following double strand breaks

t(11;18)(q21;q21) is the most frequent chromosomal aberration specifically associated with mucosa‐associated lymphoid tissue (MALT) lymphoma. The translocation fuses the API2 gene to the MALT1 gene and generates a functional API2‐MALT1 transcript. The breakpoint of the fusion gene is well characterized at the transcript level but poorly understood at the genomic level and the mechanism underlying the translocation is unknown. We identified the genomic breakpoint in 19 t(11;18)‐positive MALT lymphoma cases by polymerase chain reaction and sequencing and analysed the junctional sequences. The breakpoints were scattered in intron 7 and exon 8 of the API2 gene, and introns 4, 6, 7 and 8 of the MALT1 gene. Comparative sequence analysis between the API2‐MALT1 fusion on der(11) and the MALT1‐API2 fusion on der(18) showed extensive alterations including deletions, duplications and non‐template‐based insertions at the fusion junctions in all cases examined. An extensive sequence search failed to reveal any known sequence motifs that might be associated with chromosomal recombination or any novel consensus sequences at or near the breakpoints on both der(11) and der(18) except in one case, in which Alu repeats spanned the breakpoint of the MALT1‐API2 fusion. Our results suggest that t(11;18) may result from illegitimate non‐homologous end joining following double strand breaks.
Meakin adjuvant regimen in premenopausal patients with breast cancer

A 10‐year experience using ovarian ablation and prednisolone as adjuvant therapy for premenopausal patients with breast carcinoma, emphasizing tolerability and morbidity is reported. Thirty patients (15 aged <45 years, 15 aged ≥ 45 years; range 28–54 years) underwent mastectomy I lumpectomy with axillary clearance (with or without local irradiation) followed by ovarian irradiation and prednisolone therapy (2–5 mg three times daily for 5 years). Patients were reviewed every 3 months for the first 3 years and every 6 months thereafter. Follow‐up was between 1–5 and 10 years (median 5 years). Twenty‐four patients are still alive. Three patients stopped therapy because of side‐effects. There was a mean(s.e.m.) weight gain of 8–46(1–69) per cent on therapy. Nineteen patients have been weaned off prednisolone over a period of 0–5–7–5 months (median 2 months) and the median length of time off steroids is now 3 years (range 0–5–5 years). This regimen appears to be associated with an acceptable level of patient tolerability and a low chronic morbidity rate and should be considered as an alternative to adjuvant systemic cytotoxic therapy.
Effects of age/weight and castration on fatty acids composition in pork fat and the qualities of pork and pork fat in meishn x large white pigs.

This study investigates the effects of age/weight and castration on the fatty acid composition and the qualities of pork and pork fat. Thirty hybrid male pigs (50% Meishan x 50% Large White) were used. Fifteen were castrated within the first two days of age and the other fifteen remained entire. At 12 weeks of age, the pigs were divided into three groups, each consisting of five castrates and five boars. Animals were fed a basic standard commercial pelleted diet for 30,60 or 90 days and then slaughtered, so that the actual age of the pigs at slaughter was 114, 144 and 174 days respectively. Parameters considered for carcass quality were carcass weight, initial pH (pH45) and ultimate (final) pH (pHu), and P2 backfat thickness. For pork and pork fat qualities, the following parameters were considered: backfat firmness, slip point, sensory attributes and adipose tissue fatty acid composition.
The organization of inputs to motoneurons of the locust metathoracic leg.

1. Resistance reflexes at each joint of the leg arise from sense organs directionally sensitive to motion. Sensory impulses, acting indirectly through interneuron combinations, excite one set of motoneurons and inhibit their antagonists. 2. These resistance reflexes are not switched off during ‘voluntary’ movements elicited by touch elsewhere on the body, but instead they sum with other responses. 3. Although readily recorded in motoneurons, the resistance reflexes are mechanically so weak compared with voluntary movements that they are not a major item in the control of the leg. This applies also to posture. 4. When a voluntary movement or direct stimulation of a motoneuron causes a muscle to act against a load the reflexes upon motoneurons are quite different from those to motion caused by the same muscle. Therefore the reflex modification of walking patterns, in which legs are loaded by each other’s movements, and by the insect’s weight, cannot be analysed by a study of leg motions , although this has always been the method to date. 5. The positive feedback upon the motoneuron from receptors to loading of the muscle is exemplified in the jump. Between motoneurons to the femur muscles there are other neuronal interactions which accommodate the mechanics of the jump. 6. The angle of the tibial-tarsal joint depends upon sense organs which monitor the angle of the femoral-tibial joint. This inter-joint reflex sums with the local resistance reflex, centrally determined posture and voluntary movements. 7. The study of postsynaptic potentials (p.s.ps) makes possible a number of inferences about the nature of the interneuron pathways antecedent to the motoneurons. 8. Motoneurons to the same muscle usually have a high proportion of p.s. ps in common. Fast motoneurons have phasic properties because they have higher thresholds than the corresponding slow ones, as shown in situations where the p.s. ps are similar. 9. Motoneurons to antagonistic muscles can have synchronous p.s. ps of opposite sign. 10. The intraleg reflex in (6) is controlled by separate interneurons to the motoneurons that are excited together. 11. Study of the inputs upon groups of named motoneurons allows identification of the interneurons which act on them, and reveals that posture, elicited responses and spontaneous movements are determined by selection of different combinations of interneurons. 12. The same method, of recording simultaneously from several known central neurons can progressively reveal the unknown mechanisms by which interneurons integrate sensory input and generate coordinated responses.
Correlation of microvascular density and proliferation index in undifferentiated nasopharyngeal carcinoma

Abstract Background: Undifferentiated nasopharyngeal carcinoma is a highly malignant tumor with an endemic distribution. Several histologic parameters have been studied to provide prognostic information for patient management. Both proliferation index and microvascular density are commonly determined on such tumors, but the relationship between these two parameters has not been studied fully. Objectives: Determine the association between microvascular density and cellular proliferation in undifferentiated nasopharyngeal carcinoma. Methods: A series of 60 cases were studied in patients of Southeast Asian origin. Cellular proliferation was determined using Ki67 immunostaining, and vessel proliferation using CD31 immunostaining in terms of areas of increased staining (‘hot spots’). Ki67 results were scored on a scale of 0-4+ and CD31 results as a microvascular density/mm2. Results: The mean of the microvascular density was 22/mm2 in the Ki67-negative group (25 cases). In the Ki67- positive group (35 cases), the mean was 35/mm2. The difference between the positive and negative group was statistically significant (p <0.001). Microvascular density significantly increased as the Ki67 score increased (p<0.001). However, the ‘hot spots’ for microvascular density in tissue sections did not correspond to areas of increased cellular proliferation. Conclusion: Pathologists usually determine only one of these two prognostic factors when dealing with undifferentiated nasopharyngeal carcinoma. The proliferation index is suggested because it is easier to perform and can be done on small biopsies not to contain enough surface area for microvascular density determination.
Cohort studies: marching forward.

Because of their well-documented advantages, randomized controlled trials (RCTs) represent the gold standard for testing hypotheses in medical research. However, RCTs are not ideal for addressing certain research questions ( e.g. , the risk for renal insufficiency associated with alcohol intake). In addition, conducting a properly designed RCT often requires substantial time and resources. For these reasons, including barriers of cost and need for rapid answers, the majority of clinical research studies in the renal literature use an observational design. Although there clearly is a great need for more RCTs that are conducted in populations with kidney disease, rigorous observational studies are extremely valuable and in many circumstances yield similar results as rigorous RCTs (1). Furthermore, although RCTs are considered the gold standard for examining the efficacy of a therapy, studies of prognosis often are addressed best by cohort studies. In this first of a multipart series dedicated to reviewing clinical research methods in nephrology, after providing a brief overview of observational studies, we focus on one of the major subtypes of observational designs: The cohort study. A glossary of common terms that are used in this and subsequent sections of this series is included in Table 1. Details on other methods ( e.g. , case-control studies, RCTs) will be the subject of future reviews. View this table: Table 1. Glossary The simplest form of observational study is the case report or case series, which describes the clinical course of individuals with a particular condition or diagnosis. Such studies often highlight a single clinical condition and at times even suggest a potential biologic mechanism. In a case series, the clinician gains an appreciation of the breadth of abnormalities ( e.g. , range of proteinuria in patients with HIV-associated nephropathy) that may characterize a single disease process. Although these studies may attempt to identify factors or treatments that …
Expression of three oligosaccharide conjugates by neonatal rat dorsal root ganglion neurons: comparison with CGRP and GAP43 immunoreactivity

Adult dorsal root ganglion neurons express oligosaccharides conjugated to lipids that may be involved in cell–cell recognition, and consequently in the laminar organisation of their central terminations. This paper describes an immunohistochemical study of the developmental expression of 2 lactoseries (LA4 and LD2) and 1 globoseries (SSEA4) oligosaccharide conjugates in rats from embryonic d 19 to postnatal d 60. The expression of calcitonin gene related peptide and the growth associated protein GAP43 was also examined for comparative purposes. We found that these oligosaccharide conjugates begin to be expressed after birth, suggesting that they may be involved in maturation of the central or peripheral terminations, rather than axonal guidance.
Targeting innate immunity to downmodulate adaptive immunity and reverse type 1 diabetes

Type 1 diabetes (T1D) is characterized by specific destruction of pancreatic insulin-producing beta cells accompanied by evidence of beta-cell-directed autoimmunity such as autoreactive T cells and islet autoantibodies (IAAs). Currently, T1D cannot be prevented or reversed in humans. T1D is easy to prevent in the nonobese diabetic (NOD) spontaneous mouse model but reversing new-onset T1D in mice is more difficult. Since the discovery of the T-cell receptor in the 1980s and the subsequent identification of autoreactive T cells directed toward beta-cell antigens (eg, insulin, glutamic acid decarboxylase), the dream of antigen-specific immunotherapy has dominated the field with its promise of specificity and limited side effects. While such approaches have worked in the NOD mouse, however, dozens of human trials have failed. Broader immunosuppressive approaches (originally cyclosporine, subsequently anti-CD3 antibody) have shown partial successes (e.g., prolonged C peptide preservation) but no major therapeutic efficacy or disease reversal. Human prevention trials have failed, despite the ease of such approaches in the NOD mouse. In the past 50 years, the incidence of T1D has increased dramatically, and one explanation is the “hygiene hypothesis”, which suggests that decreased exposure of the innate immune system to environmental immune stimulants (e.g., bacterial products such as Toll-like receptor (TLR) 4-stimulating lipopolysaccharide [LPS]) dramatically affects the adaptive immune system and increases subsequent autoimmunity. We have tested the role of innate immunity in autoimmune T1D by treating acute-onset T1D in NOD mice with anti-TLR4/MD-2 agonistic antibodies and have shown a high rate of disease reversal. The TLR4 antibodies do not directly stimulate T cells but induce tolerogenic antigen-presenting cells (APCs) that mediate decreased adaptive T-cell responses. Here, we review our current knowledge and suggest future prospects for targeting innate immunity in T1D immunotherapy.