Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiemetic control: toward a new standard of care for emetogenic chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone have significantly improved the control of acute CINV, but delayed CINV remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have been approved for the prevention of both acute and delayed CINV. Palonosetron is a second-generation 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 (NK-1) receptor antagonists. Casopitant is another NK-1 receptor antagonist that is under review by the FDA after recent completion of Phase III clinical trials. The introduction of these new agents has generated revised antiemetic guidelines for the prevention of CINV. Future studies may consider the use of palonosetron, aprepitant and casopitant with other antiemetic agents (olanzapine, gabapentin, cannabinoids) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.
Melding breast and prostate cancers alter egos

Completed more than 400 years ago, The Ingenious Gentleman Don Quixote of La Mancha ranks among the greatest novels ever published. Even today, people are entranced by the timelessly delightful, although delusional, caricature of one Alonso Quijano. While the quest for honor and glory was at the crux of this chivalrous journey, Quijano’s alter ego is also symbolic of the power and frailty of the human mind. As the don’s sanity teeters between reality and ideality, it is in madness that the ego finds the strength and will to restore order to a world gone askew. Just as the quixotic transformation embodies the purity of the purpose, so does it also mirror the unique, albeit unsettling, way derangements in the genome bring a sense of order to the neoplastic process; and where genomic instability shifts the balance from vulnerability to invincibility. It is almost counterintuitive to believe that results of scientific research can increase the complexity of already complicated diseases; and nearly as difficult to comprehend is the illusion that looking backward enables us to see forward. Yet both beliefs are apparently true for cancer. Now, almost five decades since the first reports of the estrogen receptor (ER) and androgen receptor (AR) materialized [1–3], research has revealed diverse mechanisms by which hormones regulate a number of dynamic, yet delicate, processes in mammary and prostate glands. In this special focus issue of Expert Review of Endocrinology and Metabolism, numerous authors have contributed articles related to the involvement of sex steroid hormones in breast and prostate cancers. Here, the reader can learn a little about the treatment of these tumors, more about how the science of endocrinology and study of metabolism might improve our understanding of cancer, and perhaps gain a better appreciation of the complexity of cancer genomics.
Applause sign: screening utility for dementia and cognitive impairment

ABSTACT Objective: To examine the diagnostic utility of applause sign scores for the diagnosis of dementia and mild cognitive impairment. Methods: Consecutive unselected new outpatient referrals to a dedicated cognitive disorders clinic over a 12-month period were administered the clapping test. Criterion diagnosis was by usual clinic assessment using standard diagnostic criteria, blind to applause sign score. Results: Applause sign scores differed significantly (p < 0.001) between diagnostic groups (dementia, mild cognitive impairment, subjective memory complaint) and did not correlate with other cognitive screening instrument scores. Nearly three-quarters of those with an abnormal score had cognitive impairment. Applause sign score was specific but not sensitive for a diagnosis of cognitive impairment. Conclusion: The applause sign supports a diagnosis of dementia or cognitive impairment in high prevalence settings and may be useful in conjunction with other cognitive screening tests.
Long-term studies of treatments for type 2 diabetes

ABSTRACT There is a relative lack of long-term data for individual glucose-lowering therapies for the treatment of type 2 diabetes mellitus. A systematic search of published literature reporting data of approximately ≥3 years of follow-up from randomized controlled trials and their extensions was conducted. Trials to evaluate the efficacy and/or safety of glucose-lowering drugs currently approved for the treatment of adults with type 2 diabetes were included. Search results included long-term published data for traditional oral glucose-lowering drugs, insulin, α-glucosidase inhibitors, and incretin-based therapies. In general, results indicated that the short-term risk/benefit profile of these therapies is in line with longer-term evaluations. Individual results from these trials are reviewed in this report. These findings support the use of approved drug classes for longer-term treatment of type 2 diabetes.
Human Ligamentum Nuchae in the Elderly: Its Function in the Cervical Spine

Abstract The human ligamentum nuchae is commonly referenced as a site for muscle attachments in the neck, but it is rarely described as being associated with stability of the cervical spine. This descriptive anatomical study re-examines the structure of the ligamentum nuchae in the context of spinal stability and compares this information with previous studies on the structure and function of this ligament. Dissections were performed on 13 elderly cadavers to observe the attachments and fiber direction of the ligamentum nuchae. Digital photographs were taken during each phase of the dissection, and all of the parts of the ligament were observed. This observational study shows that the ligamentum nuchae has four portions: A central cord-like portion, a central septal portion, and two paired "fanlike" portions. Only the cord-like portion provides a site for muscle attachment. From these observations, the potential contributions of all portions of the ligamentum nuchae to cervical stability are discussed.
Life Course Factors Associated With Suicidal Behaviors in Young People

This article reviews the major life course factors and processes associated with the development of suicidal behaviors in young people. Key issues examined include (a) the spectrum of suicidal behaviors in young people; (b) changing risks of suicidal behavior during childhood, adolescence, and young adulthood; and (c) key risk and protective factors. It is concluded that suicidal tendencies are frequently the culmination of adverse life course sequences that involve multiple risk factors. Future research priorities include a focus on (a) greater understanding of the role of genetic and biologic factors in the development of suicidal behaviors, (b) exploration of factors that may protect young people against suicidal behaviors, and (c) evaluation of public health and clinical programs designed to minimize risk of suicidal behaviors in young people.
Transdermal estrogens in the changing landscape of hormone replacement therapy

ABSTRACT Views and clinical practice on hormone replacement therapy (HRT) for postmenopausal women have varied widely over the last several decades. The 1990s showed a dramatic decline in prescribing and only recently are prescription rates increasing again. Use of HRT is first line for women suffering from the symptoms of menopause. For a certain population of postmenopausal women, HRT is recommended for prevention of fracture. More consideration is being given to patient risk factors, side effects, and formulations available. Transdermal patch estrogen formulations have been on the market for many years and are becoming more common although many physicians are less familiar with the various options. Transdermal preparations are worth consideration with regard to less adverse effects as there is the avoidance of liver metabolism and accumulation of metabolites with antiestrogenic activity. Data suggests that transdermal patch estrogen preparations are both safer and potentially more efficacious than oral estrogen therapy. Guidelines recommend the addition of progesterone for women who have not had a hysterectomy. Transdermal patch estrogen has a role for women as a choice for individualized therapy and providers need to be familiar with the formulations as well as unique challenges and advantages.
Individualizing the selection of long-acting bronchodilator therapy for patients with COPD: considerations in primary care

ABSTRACT Chronic obstructive pulmonary disease (COPD) is a common condition encountered in primary care settings. COPD remains the third leading cause of death in the United States and carries a significant burden to both patients and the healthcare system. COPD is a chronic, progressive, irreversible lung disease associated with high morbidity and mortality. Proper assessment and diagnosis requires spirometry which is currently underutilized in primary care. Management is focused on adequate symptom control, improving quality of breathing and quality of life, and preventing exacerbations and hospitalizations. However, many patients are not receiving long-acting bronchodilator maintenance therapy as recommended in current clinical guidelines. Even when patients receive appropriate therapy, real-world issues such as a patient’s health literacy, physical and cognitive limitations, and therapy nonadherence limit the effectiveness of prescribed inhaled medications. Primary care providers are well situated to ensure that prescribed therapies and long-term management goals are matched to the individual needs of patients with COPD.
Effects of Fourth-Generation Fluoroquinolones on the Ocular Surface, Epithelium, and Wound Healing

Purpose: To compare the cellular effects of gatifloxacin and moxifloxacin on multidimensional aspects of corneal wound healing. Methods: Several animal models were used to evaluate the effect of commercial preparations of gatifloxacin ophthalmic solution 0.3% (Zymar) and moxifloxacin ophthalmic solution 0.5% (Vigamox) on the rate and quality of corneal wound healing. These included an in vivo rabbit anterior keratectomy model, a central corneal full-thickness incision model, and a model of the inflammation associated with experimental dry eye in mice. An in vitro normal human conjunctival epithelial cell culture model was also evaluated. Results: Despite the presence of benzalkonium chloride (BAK) in its formulation, gatifloxacin caused less degradation of corneal epithelial barrier function than moxifloxacin did. Moxifloxacin inhibited collagen IV synthesis to a greater extent than did gatifloxacin, and transmission electron microscopy revealed loss of normal structure in the basal lamina of moxifloxacin-treated eyes. Incisional healing in eyes treated with moxifloxacin was slower and more disorganized than in eyes treated with gatifloxacin or vehicle. In the gatifloxacin-treated cultures, the normal human conjunctival cells continued to grow and appeared most like the vehicle-treated cultures. Conversely, moxifloxacin inhibited cell proliferation. Conclusion: Taken together, the studies presented here provide evidence that moxifloxacin has a deleterious effect on both the speed and quality of corneal wound healing, whereas gatifloxacin does not. The clinical relevance of these data needs to be evaluated further.
Is Intraoperative Remifentanil Associated With Acute or Chronic Postoperative Pain After Prolonged Surgery? An Update of the Literature

Objective:Remifentanil is an ultra-short-acting opioid that is used commonly during both short-term and prolonged surgery. This review investigated associations of intraoperative remifentanil administration with acute postoperative pain, hyperalgesia, and chronic postoperative pain, with emphasis on the perioperative coanesthetic drug regimen used. Methods:Medline and Embase databases were searched for randomized studies, evaluating the intraoperative use of remifentanil (>2 h) versus another analgesic or a different dosage of remifentanil, and reporting acute postoperative pain parameters such as postoperative pain scores, hyperalgesia, acute opioid tolerance, or analgesics requirements. Furthermore, all studies in which remifentanil was used intraoperatively and parameters for chronic postoperative pain were measured were included (pain levels after a prolonged period of time after surgery). Results:From the 21 studies that were identified, less than half of the studies found higher acute postoperative pain, higher postoperative analgesic requirements after intraoperative remifentanil use, or both. Coanesthetics to some extent determined this incidence, with mainly studies using volatile agents reporting increased pain levels. There was less evidence when remifentanil was combined with total intravenous anesthesia or a combination of anesthetics. The limited number of studies (n=4) evaluating chronic pain suggested a potential association with the intraoperative use of remifentanil. Discussion:Although studies are diverse and sample sizes small, coanesthetics used in combination with remifentanil may influence the occurrence of postoperative hyperalgesia. No firm conclusions could be made regarding acute and chronic pain, indicating that further research with the goal to investigate the effect of volatile or intravenous anesthetics along with simultaneous remifentanil infusion on acute and chronic postoperative pain is needed.
Fulranumab in Patients With Pain Associated With Postherpetic Neuralgia and Postraumatic Neuropathy

Objective: Fulranumab is an antibody that specifically neutralizes the biological activity of human nerve growth factor. This multicenter, phase-2, randomized, double-blind (DB), placebo-controlled study evaluated the analgesic efficacy and safety of fulranumab in postherpetic neuralgia (PHN) and posttraumatic neuropathy (PTN) patients. Methods: Patients (18 to 80 y) with inadequately controlled moderate-to-severe pain received study medication (subcutaneous injection) every 4 weeks. PHN patients were randomized (3:2:2:3) to receive either placebo or one of 3 doses of fulranumab: 1 mg (1 mgQ4 wk), 3 mg (3 mgQ4 wk), or 10 mg (10 mgQ4 wk). PTN patients were randomized (1:1) to receive either placebo or fulranumab 10 mgQ4 wk. Results: The US Food and Drug Administration placed a clinical hold (December 23, 2010) on all trials of antinerve growth factor drugs, including fulranumab, due to identified risks of osteonecrosis or rapidly progressing osteoarthritis; therefore, only 49 (of 150 planned) PHN patients and 34 (of 50 planned) PTN patients completed the DB efficacy evaluation. There was no significant difference (P>0.05, fulranumab vs. placebo) for change in 7-day average of daily pain intensity scores from DB baseline to end of 12-week DB efficacy phase in PHN or PTN patients (primary endpoint). No significant difference was found with fulranumab versus placebo (P>0.05) in other efficacy measures in either PHN or PTN patients. The most common treatment-emergent adverse events (>10% incidence) in PTN patients were sinusitis, carpal tunnel syndrome, and headache, whereas in PHN patients it was arthralgia. Discussion: Fulranumab did not demonstrate efficacy in either PHN or PTN patients, but was generally well-tolerated in this small underpowered and abbreviated study.
Primary Pyomyositis: Its Socioeconomic Effects; A Community Overview. A Qualitative Study Design

Aims: To assess the community’s views on the socioeconomic effects of primary pyomyositis to patients, family, health facilities and community. Study Design: A cross-sectional study design using qualitative research methods Place and Duration of Study: Gulu Regional and other Hospitals in Northern Uganda from September 2011 to November 2013. Methodology: The study was conducted among patients with primary pyomyositis, next of kin, health workers and opinion leaders on their views on the socioeconomic effects of pyomyositis. Key Informant Interviews, Focus Group Discussions and In-depth Interviews were used to obtain qualitative information. Ethical approval for the study was obtained from Gulu University IRB and the National Council of Science and Technology (UNCST IJTDH, 7(4): 144-155, 2015; Article no.IJTDH. 2015.067 145 Results: Primary pyomyositis has several socioeconomic effects to patients, family, health facilities and communities. The effects of the disease ranges from simple disability to inability to earn a living thus deepening the economic status/crisis of individuals, families and communities. It creates series of social problems that make local leaders become less useful to their communities and also sets-in marriage related problems. Education of the school going children are usually affected leading to school dropout. Conclusion: There is a wide range of socioeconomic effects of primary pyomyositis to the population of Northern Uganda and it is presented with a number of socioeconomic effects similar to those chronic diseases such as HIV/AIDS.
Effects of long‐term whole‐body cold exposures on plasma concentrations of ACTH, beta‐endorphin, cortisol, catecholamines and cytokines in healthy females

Objective. Cold therapy is used to relieve pain and inflammatory symptoms. The present study was designed to determine the influence of long‐term regular exposure to acute cold temperature. Two types of exposure were studied: winter swimming in ice‐cold water and whole‐body cryotherapy. The outcome was investigated on humoral factors that may account for pain alleviation related to the exposures. Material and methods. During the course of 12 weeks, 3 times a week, a group of healthy females (n = 10) was exposed to winter swimming (water 0–2°C) for 20 s and another group (n = 10) to whole‐body cryotherapy (air −110°C) for 2 min in a special chamber. Blood specimens were drawn in weeks 1, 2, 4, 8 and 12, on a day when no cold exposure occurred (control specimens) and on a day of cold exposures (cold specimens) before the exposures (0 min), and thereafter at 5 and 35 min. Results. Plasma ACTH and cortisol in weeks 4–12 on time‐points 35 min were significantly lower than in week 1, probably due to habituation, suggesting that neither winter swimming nor whole‐body cryotherapy stimulated the pituitary‐adrenal cortex axis. Plasma epinephrine was unchanged during both experiments, but norepinephrine showed significant 2‐fold to 3‐fold increases each time for 12 weeks after both cold exposures. Plasma IL‐1‐beta, IL‐6 or TNFα did not show any changes after cold exposure. Conclusions. The main finding was the sustained cold‐induced stimulation of norepinephrine, which was remarkably similar between exposures. The frequent increase in norepinephrine might have a role in pain alleviation in whole‐body cryotherapy and winter swimming.
Role of the fractalkine receptor CX3CR1 polymorphisms V249I and T280M as risk factors for early‐onset coronary artery disease in patients with no classic risk factors

Objectives. CX3CR1 is a monocyte chemokine receptor and adhesion molecule. Two CX3CR1 mutations, V249I and T280M, reportedly decrease coronary artery disease (CAD) risk independent of established risk factors. An I249 protective effect is attributed to reducing CX3CR1 binding to fractalkine, its ligand. Material and methods. We examined the frequencies of V249I and T280M among early‐onset CAD patients (G1; n = 149; <50 years), late‐onset CAD patients (G2; n = 150; >65 years) and healthy controls (HC; n = 149, 47–93 years) without known CAD risk factors. We compared plasma total cholesterol (TC)/high density lipoprotein‐C (HDL‐C) and apolipoprotein B (APOB)/apolipoprotein AI (APOAI) ratios among the groups and mutation carriers and non‐carriers, and the prevalence of the mutations in G1 and G2 patients with multiple coronary vessel disease (MVD) and myocardial infarction (MI). Results. G1 patients had non‐significantly lower frequencies of I249 versus (vs.) G2 or controls (G1; 51 %, G2: 61 %, controls: 58 %, p = 0.19), with no difference in T280M (p = 0.8). TC/HDL‐C and APOB/APOAI ratios were significantly higher in G1 patients vs. G2 and controls (p<0.0001) independently of either mutation. More G2 patients had MVD than younger ones (p<0.0001); however, more G1 patients were homozygous for V249 compared to G2 patients, who more often had the I249 allele (p<0.02). There was no such association with T280M (p = 0.38). Although more G1 patients had MI, this was not mutation related. Conclusions. There were significantly higher lipid ratios in G1 compared to G2 and HC (G1>G2>HC), but not in mutation prevalence. I249 mutation was associated with MVD in older patients, while V249 homozygosity was associated with the early‐onset CAD. Neither allele affected MI or lipid levels.
Circulating serum trefoil factors increase dramatically during pregnancy

Objective. Trefoil factors (TFF1–3) are 7–12 kDa peptides secreted by mucosal surfaces, with changing levels of expression reflected in serum concentrations. The genes for the peptides are located on chromosome 21, the chromosome duplicated in trisomy 21. We studied the levels of circulating TFFs in pregnant women carrying trisomy 21 foetuses and in women with normal pregnancies, throughout pregnancy and postpartum. Material and methods. Employing ELISA methods, serum collected at gestational weeks (GW) 18, 32, 39 and 8 weeks postpartum from women carrying normal foetuses (n = 141) was analysed for TFFs. In addition, serum collected at GW 6–14 (median = 10) from women carrying trisomy 21 foetuses (n = 48) or healthy foetuses (n = 46) was analysed. Results. Peaking at 39 GW, concentrations of TFF2 and TFF3 were 3.5 and 47 times higher, respectively, than postpartum. Postpartum levels were comparable to concentrations previously measured in non‐pregnant women. TFF1 concentrations rose throughout pregnancy and postpartum, being 1.5 times higher postpartum compared to 18 GW. No differences in the levels of TFFs were observed between women carrying trisomy 21 and those with healthy foetuses. To our knowledge, circulating TFF3 has never been reported to reach the levels observed here. Also, the pattern of increase is unusual, as previous reports have shown parallel increases in TFF1 and TFF3 with no alterations in TFF2. Conclusions. Our results demonstrate that circulating TFFs are not candidate markers of trisomy 21 in first‐trimester pregnancies, but raise intriguing questions concerning the origin of TFFs produced during pregnancy and their physiological function.
Successful treatment of female‐pattern hair loss with spironolactone in a 9‐year‐old girl

A 9‐year‐old prepubertal girl with female pattern hair loss treated with spironolactone 100 mg orally per day had objective improvement demonstrated by regrowth observed clinically and on comparison of pre‐ and post‐treatment stereotactic scalp photographs taken 6 months apart.