Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Case of Bisphosphonate-Related Osteonecrosis of the Torus Palatinus in a Patient with Metastatic Breast Cancer

Bisphosphonates administered orally and intravenously are used for a variety of endocrine and oncologic indications. Long-term intravenous use of bisphosphonates has been shown to cause osteonecrosis of the jaw. We report a case in which a 58-year-old woman with metastatic breast cancer received 18 doses of 4 mg intravenous zoledronic acid over a period of 16 months and developed a region of osteonecrosis on the posterior edge of a large, lobular torus palatinus. Torus palatinus, a type of maxillary exostosis, is common among postmenopausal women, and is vulnerable to blunt trauma that could predispose to osteonecrosis. Sequestrum of dead bone was removed and the site healed within 4 weeks. This case demonstrates that patients with a torus palatinus may be at high risk for osteonecrosis, and reinforces the need for good oral hygiene and frequent dental examination while receiving bisphosphonate therapy.
Analytical Determination of DC-Bus Utilization Limits in Multiphase VSI Supplied AC Drives

Two-level multiphase voltage source inverters (VSIs) are typically used as the supply for multiphase machines. Such machines are often with concentrated winding in which case, certain low-order stator current harmonics are injected to provide torque enhancement. Also, a multimotor drive system can be realized by connecting a number of multiphase machines in series, using phase transposition while supplying the whole system from a single multiphase VSI. In both situations, it is important to know the limits of the inverter operation in the linear modulation region. This paper develops a simple method that enables analytical determination of the boundaries of the linear modulation region for all multiphase inverters with a prime number of phases. The limits are independent of the actual pulse width modulation (PWM) method utilized, and are equally applicable to both carrier-based and space vector PWM techniques. Theoretical considerations are verified experimentally using the five-phase and seven-phase VSI rigs.
Age at natural menopause and factors associated with menopause state among Puerto Rican women aged 40-59 years, living in Puerto Rico

Objective:The timing of menopause is associated with multiple health outcomes in female populations including all-cause mortality, heart disease, breast cancer, and osteoporosis. Although research suggests that age at menopause varies in different ethnic groups, data on age at menopause among Hispanic women are limited. Design:The present cross-sectional study estimates age at natural menopause among a sample of 1,272 Puerto Rican women aged 40 to 59 years who participated in health fairs held in 22 municipalities of Puerto Rico between May 2000 and November 2001. Cox proportional hazard regression analysis was used to characterize age at natural menopause and its association with relevant covariates. Results:The overall adjusted median age at natural menopause was 51.3 years. Current employment (hazard ratio = 0.75, 95% CI: 0.59-0.95) and parity of two or three children as compared with having no children or one child (hazard ratio = 0.73, 95% CI: 0.54-0.98) were associated with a later menopause. Conclusions:This study provides a robust estimate of age at menopause for Puerto Rican women, which is similar to overall estimates previously reported for US populations, but higher than estimates for other Hispanic populations. Our results confirm attributes associated with age at menopause and provide information relevant to understanding the potential chronic disease burden of Puerto Rican women as they age.
Involvement of CD44 in matrix metalloproteinase‐2 regulation in human melanoma cells

CD44 is a family of cell‐surface‐adhesion proteins that are thought to play an important role in cancer invasion and metastasis. However, the specific mechanisms by which CD44 expression modulates invasion or metastasis are not well understood. In the current study, we have demonstrated that treatment of human melanoma cells with a CD44 MAb, F10‐44‐2, induces up‐regulation of matrix metalloproteinase‐2 (MMP‐2) protein and mRNA. Moreover, treatment of melanoma cells with MAb F10‐44‐2 enhances their migration through gelatin‐coated membranes and invasion through reconstituted basement membranes. Treatment of melanoma cells with several known CD44 ligands, including hyaluronate, extracellular‐matrix proteins, and osteopontin, did not induce MMP‐2 production. CD44 binding by F10‐44‐2 MAb results in induction of MMP‐2 expression, which is associated with enhanced cell migration and invasion. These findings have several implications for investigations into tumor metastasis, development, and lymphocyte function. Int. J. Cancer 80:387–395, 1999. © 1999 Wiley‐Liss, Inc.
Increased intestinal protein permeability in a model of lung injury induced by phorbol myristate acetate.

Multiple nonpulmonary organ failure is a frequent complication of the adult respiratory distress syndrome (ARDS), and contributes significantly to the high mortality rate associated with this disorder. Although previous studies suggest that systemic organ injury may be an integral component of ARDS, little is known about the specific functional alterations that occur in these target organs. The present study was designed, therefore, to test the hypothesis that endothelial damage, as assessed by microvascular permeability changes, develops in systemic organs in a model of acute lung injury. To test this postulate, the microvascular permeability for total protein was estimated using the steady-state relationship between the lymph (CL) to plasma (Cp) protein concentration ratio (i.e., CL/Cp) and lymph flow in autoperfused cat ileum preparations. Specifically, CL/Cp was measured in five cats, 2 h after acute lung injury was induced by intravenously administered phorbol myristate acetate (PMA), 15 micrograms/kg, and the results were compared with those of seven time-matched control animals. Prior to PMA infusion, the PaO2/FIO2 ratio was 451 +/- 28 in both groups and remained unchanged (486 +/- 26) in the control group. By contrast, the PaO2/FIO2 ratio fell to 275 +/- 95 after PMA infusion (p less than 0.05). In addition, whereas CL/Cp was 0.099 +/- 0.008 in the control animals, it increased to 0.36 +/- 0.06 in the PMA-injured animals (p less than 0.01). In summary, this study demonstrated that in this model of acute lung injury produced by PMA-induced activation of circulating inflammatory cells, both acute lung injury and systemic organ injury (i.e., morphologic and permeability alterations) occurred.
Moesin: a potential LPS receptor on human monocytes

Bacterial endotoxin (lipopolysaccharide, LPS), a glycolipid found in the outer membrane of Gram-negative bacteria, induces the secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, and IL-6 by monocytes/macrophages. The secretion of these biologically active compounds leads to multiple pathological conditions, such as septic shock. There is substantial evidence that chronic exposure to LPS in periodontal diseases mediates, at least in part, the tissue destruction associated with the Gram-negative infection. LPS receptor has been shown to be CD14, a 55 kDa protein. LPS—CD14 interactions mediate many monocyte/macrophage functions in the inflammatory response. However, CD14 lacks a cytoplasmic domain, or any known signal transduction sequence motif, suggesting the existence of another cell surface domain capable of transducing signals. More recently, significant work has implicated Toll proteins in LPS-mediated signaling. The purpose of the present work was to investigate, identify, and characterize secondary LPS binding cell surface domain(s) on monocytes/macrophages. Initial experiments with anti-CD14 blocking antibody revealed only partial blocking of the LPS induced TNF-α response. The kinetics of these experiments suggested a second, low-affinity receptor. Cross-linking experiments were performed to identify LPS binding sites. Two domains were identified: a 55 kDa protein which was inhibited by anti-CD14 (presumably the CD14 receptor) and a second 78 kDa domain. Partial protein sequencing of the 78 kDa domain using mass spectroscopic analysis ascribed this domain to Moesin (membrane organizing extension spike protein). Preliminary experiments using anti-Moesin monoclonal antibody revealed a dose-dependent blocking of LPS induced TNF-α response with a total blocking at 50 µg/ml. Irrelevant isotype controls had no effect. Additional experiments were performed to evaluate the specificity of the anti-Moesin blocking. Separate experiments evaluated anti-Moesin effects on monocyte chemotaxis, IL-1 production in response to IL-1 stimulation, and TNF-α secretion in response to Staphylococcus aureus stimulation. Anti-Moesin antibody only blocked LPS-mediated events. Histological analysis of tissue sections harvested from LPS-induced skin lesions exhibited a 3-fold reduction of the polymorphonuclear neutrophil infiltrate in Moesin-deficient mice compared to wild type mice. The data suggest that Moesin functions as an independent LPS receptor on human monocytes.
Haemonchus contortus: characterization of a glutamate binding site in unselected and ivermectin-selected larvae and adults.

A specific ivermectin-sensitive, glutamate binding site has been identified in the parasitic nematode Haemonchus contortus. Glutamate binding in H. contortus was saturable and occurred in a single class of high-affinity binding sites which appeared to have pharmacological properties different from those of mammalian glutamate receptors. Adult and larval forms of H. contortus had dramatically different glutamate binding kinetics, the larvae showing nearly up to 200-fold higher Bmax values and up to 9-fold increases in Kd values compared to adults. Treatment of adult H. contortus with the anthelmintic, ivermectin, decreased the Bmax value for glutamate binding in the susceptible strain but not in the resistant parasites. Furthermore, selection for ivermectin resistance was associated with a significant increase in Bmax for glutamate binding in adults and a similarly significant increase in glutamate binding affinity in larvae. These results suggest that the H. contortus glutamate binding site identified in this study may be involved in the phenomenon of ivermectin resistance.
Risk Stratification in Paragangliomas with PASS (Pheochromocytoma of the Adrenal Gland Scaled Score) and Immunohistochemical Markers.

INTRODUCTION Paragangliomas (PGLs) are rare tumours that arise in sympathetic and parasympathetic paraganglia and are derived from neural crest cells. Presence of metastasis is the only absolute criterion for malignancy. There is no single histo-morphological feature indicating malignant potential and multiple parameters have been proposed to prognosticate the individual case. This includes studies conducted using Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Immunohistochemical (IHC) markers. AIM We have studied ten cases of paraganglioma and attempted to correlate the prognosis with multiple clinicopathological variables. MATERIALS AND METHODS This study was done in a tertiary care general hospital over a period of five years. Available clinical records and histopathology slides of all patients were reviewed. Using Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), we divided the cases into two groups-tumours showing high risk behaviour (PASS≥4) and tumours showing benign behaviour (PASS<4). IHC analysis was done using synaptophysin, chromogranin, S100 and Ki67. We correlated S100 immunoreactivity and Ki67 proliferative index with PASS score. Both PASS score and IHC markers were also correlated with clinical outcome. RESULTS There were six Pheochromocytomas (PHC) and four Paragangliomas (PGL). Two paragangliomas were retroperitoneal and one each was located in ear (HNPGL) and broad ligament. PASS score was ≥4 in five cases and <4 in five cases. Out of five cases in which PASS was ≥4, three cases showed clinical evidence of malignancy and two cases were benign. All the cases in which PASS was <4 were clinically benign. S100 immunoreactivity was grade 1 in two cases, grade 2 in six cases and grade 3 in two cases. The cases in which S100 immunoreactivity was grade 1 were malignant. One case in which S100 was grade 2 was clinically malignant. Ki67 labeling index was raised (>3%) in two cases, which were malignant correlated with malignant PASS score. CONCLUSION We conclude that the following clinicopathological parameters should be taken into account for risk assessment of malignant behaviour of paragangliomas- location, size, PASS score, S100 immunoreactivity and Ki67 labeling index.
Physicians’ experiences with patients who transgress boundaries

AbstractBACKGROUND: Boundary violations have been discussed in the literature, but most studies report on physician transgressions of boundaries or sexual transgressions by patients. We studied the incidence of all types of boundary transgressions by patients and physicians’ responses to these transgressions. METHODS: We surveyed 1,000 members of the Society of General Internal Medicine (SGIM) for the number of patient transgressions of boundaries which had occurred in the previous year. Categories were created by the investigators based on the literature. Physicians picked the most important transgression, and then were asked about their response to the transgression and its effect on the patient-physician relationship. Attitudinal questions addressed the likelihood of discharging patients who transgressed boundaries. The impact of demographic variables on the incidence of transgressions was analyzed using analysis of variance. RESULTS: Three hundred thirty (37.5%) randomly selected SGIM members responded to the survey. Almost three quarters of the respondents had patients who used their first name, while 43% encountered verbal abuse, 39% had patients who asked personal questions, 31% had patients who were overly affectionate, and 27% encountered patients who attempted to socialize. All other transgressions, including physical abuse and attempts at sexual contact, were uncommon. Only gender affected the incidence of transgressions; female physicians encountered more personal questions (P=.001), inappropriate affection (P < .005), and sexually explicit language (P < .05) than male physicians and responded more negatively to boundary transgressions. Respondents dealt with transgressions by discussion with the patient or colleagues or by ignoring the incident, but such transgressions generally had a negative impact on the relationship. Most physicians would discharge patients who engaged in physical abuse or attempts at sexual contact, but were more tolerant of verbal abuse and overly affectionate patients. CONCLUSIONS: Boundary transgressions by patients is common, but usually involves more minor infractions. Female physicians are more likely to encounter certain types of transgressions. The incidence and outcomes of such transgressions are important in assisting physicians to deal effectively with this issue.
Isolation and characterization of fra-2, an additional member of the fos gene family.

Antiserum raised against a Fos peptide (amino acids Lys-127 to Arg-140 of chicken c-Fos) recognizes a 46-kDa Fos-related protein in cell lysates of growth-stimulated chicken embryo fibroblasts. Induction of the 46-kDa protein is transient but is slightly prolonged relative to c-Fos following growth stimulation. Using a mixed oligonucleotide probe encoding the peptide antigen, we have cloned the chicken genomic locus that encodes this protein and have determined its gene structure. This locus consists of four exons, each of which has some homology with the corresponding exons of the chicken c-fos gene, and it expresses a 6-kilobase mRNA after growth stimulation. The deduced amino acid sequence of the gene (323 amino acids) contains a "leucine zipper" and includes five distinct regions that exhibit strong sequence homology to the recently identified fos-related antigens Fra-1 (rat) and FosB (mouse) as well as c-Fos. Since the other regions of the gene have little homology to any of these three proteins, this gene was named "fra-2. " When the fra-2 gene was overexpressed by an avian retrovirus vector, it caused transformation of chicken embryo fibroblasts. The fra-2 gene product formed a complex in cells with the c-Jun protein, indicating that c-fos and fra-2 share biological and biochemical functions.
Oxidative stress does not influence local sweat rate during high‐intensity exercise

What is the central question of this study? We evaluated whether oxidative stress attenuates the contribution of nitric oxide to sweating during high‐intensity exercise. What is the main finding and its importance? In contrast to our previous report of an oxidative stress‐mediated reduction in nitric oxide‐dependent cutaneous vasodilatation in this cohort during intense exercise, we demonstrated no influence of local ascorbate administration on the sweating response during moderate‐ (∼51% peak oxygen uptake) or high‐intensity exercise (∼72% peak oxygen uptake). These new findings provide important mechanistic insight into how exercise‐induced oxidative stress impacts sudomotor activity.
Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02.

Between March 1984 and July 1988, 1,158 patients with Dukes' A, B, and C carcinoma of the colon were entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-02. Patients were randomized to either no further treatment following curative resection or to postoperative fluorouracil (5-FU) and heparin administered via the portal vein. Therapy began on day of operation and consisted of constant infusion for 7 successive day. Average time on study was 41.8 months. A comparison between the two groups of patients indicated both an improvement in disease-free survival (74% v 64% at 4 years, overall P = .02) and a survival advantage (81% v 73% at 4 years, overall P = .07) in favor of the chemotherapy-treated group. When compared with the treated group, patients who received no further treatment had 1.26 times the risk of developing a treatment failure and 1.25 times the likelihood of dying after 4 years. Particularly significant was the failure to demonstrate an advantage from 5-FU in decreasing the incidence of hepatic metastases. The liver was the first site of treatment failure in 32.9% of 82 patients with documented recurrences in the control group and in 46.3% of 67 patients who received additional treatment. Therapy is administered via a regional route to affect the incidence of recurrence within the perfused anatomic boundary. Since, in this study, adjuvant portal-vein 5-FU infusion failed to reduce the incidence of hepatic metastases, it may be concluded that its use thus far is not justified. It may also be speculated that the disease-free survival and survival advantages (the latter of borderline significance) are a result of the systemic effects of 5-FU.
Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion.

BACKGROUND Striated muscle has been shown to be capable of taking up and expressing foreign genes transferred in the form of naked plasmid DNA, although typically with a low level of gene expression. In the case of genes that encode secreted proteins, however, low transfection efficiency may not preclude bio-activity of the secreted gene product. Accordingly, we investigated the hypothesis that intramuscular (IM) gene therapy with naked plasmid DNA encoding vascular endothelial growth factor (VEGF) could augment collateral development and tissue perfusion in an animal model of hindlimb ischemia. METHODS AND RESULTS Ten days after ischemia was induced in one rabbit hindlimb, 500 micrograms of phVEGF165, or the reporter gene LacZ, was injected IM into the ischemic hindlimb muscles. Thirty days later, angiographically recognizable collateral vessels and histologically identifiable capillaries were increased in VEGF transfectants compared with controls. This augmented vascularity improved perfusion to the ischemic limb, documented by a superior calf blood pressure ratio for phVEGF165 (0.85 +/- 0.05) versus controls (0.64 +/- 0.05, P < .01), improved blood flow in the ischemic limb (measured with an intra-arterial Doppler wire) at rest (phVEGF165 = 21.3 +/- 3.9 mL/min, control = 14.6 +/- 1.6 mL/min, P < .01) and after a vasodilator (phVEGF165 = 54.2 +/- 12.0 mL/min, control = 37.3 +/- 8.9 mL/min, P < .01) and increased microspheres in the adductor (phVEGF165 = 4.3 +/- 1.6 mL.min-1.100 g of tissue-1, control = 2.9 +/- 1.2 mL.min-1.100 g of tissue-1, P < .05) and gastrocnemius (phVEGF165 = 3.9 +/- 1.0 mL.min-1.100 g of tissue-1, control = 2.8 +/- 1.4 mL.min-1.100 g of tissue-1, P < .05) muscles of the ischemic limb. CONCLUSIONS Ischemic skeletal muscle represents a promising target for gene therapy with naked plasmid DNA. IM transfection of genes encoding angiogenic cytokines, particularly those that are naturally secreted by intact cells, may constitute an alternative treatment strategy for patients with extensive peripheral vascular disease in whom the use of intravascular catheter-based gene transfer is compromised and/or prohibited.
More than an intervention: strategies for increasing diversity and inclusion in STEM

Purpose This paper aims to provide insight into the strategies used by leaders of graduate school preparation programs for science, technology, engineering and mathematics (STEM) to recruit and retain graduate students of color within STEM fields. Design/methodology/approach This paper is a qualitative multiple-case study using a snowball sample and semi-structured interview protocol. Twenty interviews were conducted. Findings Graduate program leaders use particular strategies to increase diversity and inclusion within graduate STEM education, and these strategies are strongly influenced by their institutional context. The most common strategies include collaboration, mapping the political terrain, evaluation, mediation, persistence, persuasion, networking in and outside of the institution, strategic planning, bargaining and negotiation, reaching out to the greater campus, and coalition building and developing allies. Research limitations/implications All of the institutions in this study were public research institutions. Further inquiry is needed on more diverse types of institutions. Practical implications The results of this study can be used by institutional and STEM program leaders who wish to increase diversity and inclusion. Social implications This research study raises awareness about an under-studied group of leaders, as well as the importance of considering context when developing strategic plans for increasing diversity and inclusion for STEM. Originality/value This study is unique because while graduate school preparation programs have become an important strategy for addressing diversity in STEM fields, research on these programs usually focuses only on student outcomes. This study provides rare insight into what is required to implement, sustain and expand these kind of diversity programs.