anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Teratogenic Effects: Pregnancy Category C.

There are no adequate and well-controlled studies of ESBRIET in pregnant women. Pirfenidone was not teratogenic in rats and rabbits. Because animal reproduction studies are not always predictive of human response, ESBRIET should be used during pregnancy only if the benefit outweighs the risk to the patient.

A fertility and embryo-fetal development study with rats and an embryo-fetal development study with rabbits that received oral doses up to 3 and 2 times, respectively, the maximum recommended daily dose (MRDD) in adults (on mg/m2 basis at maternal doses up to 1000 and 300 mg/kg/day, respectively) revealed no evidence of impaired fertility or harm to the fetus due to pirfenidone. In the presence of maternal toxicity, acyclic/irregular cycles (e.g., prolonged estrous cycle) were seen in rats at doses approximately equal to and higher than the MRDD in adults (on a mg/m2 basis at maternal doses of 450 mg/kg/day and higher). In a pre- and post-natal development study, prolongation of the gestation period, decreased numbers of live newborn, and reduced pup viability and body weights were seen in rats at an oral dosage approximately 3 times the MRDD in adults (on a mg/m2 basis at a maternal dose of 1000 mg/kg/day).
It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.
BACKGROUND: Weight stigma is increasingly common in early adolescence and may lead to weight bias internalization, with negative consequences for mental health outcomes. This study aimed to: examine the relations of perceived weight stigma and internalized weight bias with early adolescents' internalizing symptoms and disordered eating behavior; explore the mediating role of internalized weight bias on the relations of perceived weight stigma with internalizing symptoms and disordered eating behaviors; examine body esteem as a mediator between internalized weight bias and mental health outcomes.
METHODS: A sample of 406 early adolescents (59.6% girls) aged between 11 and 13 participated in this cross-sectional study. They completed self-report measures assessing perceived weight stigma, internalized weight bias, body esteem, internalizing symptoms and disordered eating.
RESULTS: Path analysis indicated that perceived weight stigma was positively related with internalizing symptoms and internalized weight bias. Further, internalized weight bias was negatively related with body esteem and positively related with internalizing symptoms and disordered eating. Internalized weight bias mediated the relations of perceived weight stigma with internalizing symptoms, disordered eating and body esteem. Further, body esteem mediated the relations of internalized weight bias with internalizing symptoms and disordered eating behavior.
CONCLUSIONS: The findings highlight internalized weight bias as a psychological mechanism potentially explaining negative links of weight stigma with internalizing symptoms and disordered eating in early adolescence. The results emphasize the need for early intervention during this developmental stage, in order to prevent psychological and behavioral outcomes of weight stigma and internalized weight bias.
Teratogenic Effects, Pregnancy Category C

In animal reproduction studies, duloxetine has been shown to have adverse effects on embryo/fetal and postnatal development. 

When duloxetine was administered orally to pregnant rats and rabbits during the period of organogenesis, there was no evidence of teratogenicity at doses up to 45 mg/kg/day (7 times the maximum recommended human dose [MRHD, 60 mg/day] and 4 times the human dose of 120 mg/day on a mg/m2 basis, in rat; 15 times the MRHD and 7 times the human dose of 120 mg/day on a mg/m2 basis in rabbit). However, fetal weights were decreased at this dose, with a no-effect dose of 10 mg/kg/day (2 times the MRHD and ≈1 times the human dose of 120 mg/day on a mg/m2 basis in rat; 3 times the MRHD and 2 times the human dose of 120 mg/day on a mg/m2 basis in rabbits). 

When duloxetine was administered orally to pregnant rats throughout gestation and lactation, the survival of pups to 1 day postpartum and pup body weights at birth and during the lactation period were decreased at a dose of 30 mg/kg/day (5 times the MRHD and 2 times the human dose of 120 mg/day on a mg/m2 basis); the no-effect dose was 10 mg/kg/day. Furthermore, behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity, were observed in pups following maternal exposure to 30 mg/kg/day. Post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment. 

There are no adequate and well-controlled studies in pregnant women; therefore, duloxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 

Nonteratogenic Effects

Neonates exposed to SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see WARNINGS AND PRECAUTIONS ( 5.4 )]. 

When treating pregnant women with duloxetine during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering duloxetine in the third trimester [see DOSAGE AND ADMINISTRATION ( 2.3 )].
PURPOSE OF REVIEW: To examine the epidemiological data on obesity and leukemia; evaluate the effect of obesity on leukemia outcomes in childhood acute lymphoblastic leukemia (ALL) survivors; assess the potential mechanisms through which obesity may increase the risk of leukemia; and provide the effects of obesity management on leukemia. Preventive (diet, physical exercise, obesity pharmacotherapy, bariatric surgery) measures, repurposing drugs, candidate therapeutic agents targeting oncogenic pathways of obesity and insulin resistance in leukemia as well as challenges of the COVID-19 pandemic are also discussed.
RECENT FINDINGS: Obesity has been implicated in the development of 13 cancers, such as breast, endometrial, colon, renal, esophageal cancers, and multiple myeloma. Leukemia is estimated to account for approximately 2.5% and 3.1% of all new cancer incidence and mortality, respectively, while it represents the most frequent cancer in children younger than 5 years. Current evidence indicates that obesity may have an impact on the risk of leukemia. Increased birthweight may be associated with the development of childhood leukemia. Obesity is also associated with worse outcomes and increased mortality in leukemic patients. However, there are several limitations and challenges in meta-analyses and epidemiological studies. In addition, weight gain may occur in a substantial number of childhood ALL survivors while the majority of studies have documented an increased risk of relapse and mortality among patients with childhood ALL and obesity. The main pathophysiological pathways linking obesity to leukemia include bone marrow adipose tissue; hormones such as insulin and the insulin-like growth factor system as well as sex hormones; pro-inflammatory cytokines, such as IL-6 and TNF-α; adipocytokines, such as adiponectin, leptin, resistin, and visfatin; dyslipidemia and lipid signaling; chronic low-grade inflammation and oxidative stress; and other emerging mechanisms. Obesity represents a risk factor for leukemia, being among the only known risk factors that could be prevented or modified through weight loss, healthy diet, and physical exercise. Pharmacological interventions, repurposing drugs used for cardiometabolic comorbidities, and bariatric surgery may be recommended for leukemia and obesity-related cancer prevention.
Each subject will receive a single dose of 2 inhaled doses from Indacaterol/glycopyrronium Easyhaler product variant A in one of the four periods (cross-over) with concomitant charcoal administration (Carbomix granules). The total dose is 170 µg of indacaterol and 86 µg glycopyrronium (delivered doses).
The invention discloses externally-applied traditional Chinese medicine having the effects of detoxicating and destroying parasites, eliminating stagnation and durable and non-convergent ulcer, promoting tissue regeneration and activating blood. The traditional Chinese medicine is prepared from realgar, alums, calomel, frankincense, centipede, long-noded pit viper, mercury, croton seed and saltpeter. Based on the principles of clearing away heat and toxic materials, diminishing inflammation, dissipating stasis, sterilizing, promoting tissue regeneration and promoting blood circulation to remove meridian obstruction, calomel, frankincense, realgar, centipede and mercury are mainly selected for removing and counteracting toxic substances, regulating qi, activating blood, activating meridians to stop pain and removing stasis. Long-noded pit viper, alums, croton seed and saltpeter are taken as auxiliary medicaments for dredging collaterals, relieving convulsion, resisting bacteria, activating blood, treating cold stagnation and removing stasis. Calomel, frankincense, realgar, centipede and mercury have the effects of removing damp toxins, counteracting toxic substances, tracing toxins and activating meridians to stop pain; and long-noded pit viper, alums, croton seed and saltpeter have the effects of dredging collaterals, relieving convulsion, stopping bleeding, dissipating stasis, diminishing inflammation and eliminating swelling. A plurality of medicaments take effect together at a high temperature, better effects of counteracting toxic substances, removing stasis, dredging collaterals, activating blood and promoting tissue regeneration are achieved, and the pain of surgery and sequelae is eliminated, so that the aim of treating both symptoms and root causes is fulfilled.
Medical training is notoriously stressful. The combination of long work hours, sleep deprivation, clinical responsibilities, and academics leaves little time for residents and fellows to consider their own health maintenance, particularly with regards to physical activity. This is problematic for both the physician and the physician's patients. Numerous studies have shown that physicians who exercise regularly and maintain normal body mass are more likely to counsel their patients on these issues. Additionally, they are more experienced in the benefits of exercise and can counsel their patients on how to incorporate exercise into a busy schedule. This is a one year follow up survey study after a Fitbit® challenge study among TriHealth residents. The purpose of the initial Fitbit® challenge study was to to determine if wearing a Fitbit® motivates residents to increase their physical activity. This study seeks to determine the long-term usage of the Fitbit®.
Efavirenz: Long-term carcinogenicity studies in mice and rats were carried out with efavirenz. Mice were dosed with 0, 25, 75, 150, or 300 mg/kg/day for 2 years. Incidences of hepatocellular adenomas and carcinomas and pulmonary alveolar/bronchiolar adenomas were increased above background in females. No increases in tumor incidence above background were seen in males. In studies in which rats were administered efavirenz at doses of 0, 25, 50, or 100 mg/kg/day for 2 years, no increases in tumor incidence above background were observed. The systemic exposure (based on AUCs) in mice was approximately 1.7-fold that in humans receiving the 600-mg/day dose. The exposure in rats was lower than that in humans. The mechanism of the carcinogenic potential is unknown. However, in genetic toxicology assays, efavirenz showed no evidence of mutagenic or clastogenic activity in a battery of in vitro and in vivo studies. These included bacterial mutation assays in S. typhimurium and E. coli, mammalian mutation assays in Chinese hamster ovary cells, chromosome aberration assays in human peripheral blood lymphocytes or Chinese hamster ovary cells, and an in vivo mouse bone marrow micronucleus assay. Given the lack of genotoxic activity of efavirenz, the relevance to humans of neoplasms in efavirenz-treated mice is not known.

Efavirenz did not impair mating or fertility of male or female rats, and did not affect sperm of treated male rats. The reproductive performance of offspring born to female rats given efavirenz was not affected. As a result of the rapid clearance of efavirenz in rats, systemic drug exposures achieved in these studies were equivalent to or below those achieved in humans given therapeutic doses of efavirenz.
BACKGROUND: Identifying rheumatoid arthritis patients at higher risk of complications after total hip arthroplasty could make perioperative management more effective. Here we examined whether disease activity is associated with risk of such complications.
METHODS: We retrospectively analyzed data for 337 rheumatoid arthritis patients at our medical center who underwent primary total hip arthroplasty. Rheumatoid arthritis patients were categorized according to the simplified disease activity index (SDAI), the values of which at admission and follow-up were averaged together. Logistic regression was used to examine associations of mean SDAI with rates of dislocation, infection, periprosthetic fracture and aseptic loosening. As controls, 337 osteoarthritis patients who did not have systemic inflammation and who underwent the same procedure were matched across numerous clinicodemographic variables.
RESULTS: Among the 337 rheumatoid arthritis patients, 38 (11.3%) had postoperative complications, the rates of which varied significantly from 0 to 17.5% (p = 0.003) among the four subgroups whose disease activity based on mean SDAI was categorized as high, moderate, low or in remission. Each 1-unit increase in mean SDAI was associated with a significant increase in risk of postoperative complications (OR 1.015, 95% CI 1.001-1.029, p = 0.035). Across all rheumatoid arthritis patients, rate of complications did not differ significantly between patients who received disease-modifying anti-rheumatic drugs or other treatments. Rates of dislocation, of infection or of all postoperative complications combined were significantly lower among osteoarthritis controls than among rheumatoid arthritis patients.
CONCLUSION: Greater mean SDAI is associated with higher risk of dislocation, infection and composite postoperative complications after total hip arthroplasty in rheumatoid arthritis patients. These patients show a significantly higher rate of postoperative complications than osteoarthritis patients, likely reflecting the influence of systemic inflammation. Disease activity should be reduced as much as possible in rheumatoid arthritis patients before they undergo total hip arthroplasty.
PCT No. PCT/GB90/01279 Sec. 371 Date Feb. 6, 1992 Sec. 102(e) Date Feb. 6, 1992 PCT Filed Aug. 14, 1990 PCT Pub. No. WO91/02763 PCT Pub. Date Mar. 7, 1991.Linear chain extended poly(alkylene oxides) having at least a portion of hydrophobic hydrogen bonding chain extending groups are soluble in at least one solvent and swellable in water. The chain extending groups preferably comprise a urea linkage and can be produced by the reaction of an amine with an isocyanate. The extended polymers and their solutions may readily be fabricated into controlled release compositions, e.g. for the release of pharmaceuticals.
A composition suitable for reducing or alleviating stress, comprising one or more plant stem cell extracts (apical shoots, cambium, root apical meristems) and one or more flower essences. The stem cells may be from monocot and dicot flowering plants, shrubs, trees. The flower essences may be from the flowers as defined herein, which may be from 0.1-15% by volume. The composition may comprise one or more secondary flower essences, as defined herein, which may be from 0.5-15% by volume. The composition may comprise one or more essential oils, as defined herein, which may be from 0.05-5% by volume. The composition may be an aqueous-based extract, or may be a cream. The composition may comprise one or more berry extracts, which may be maiqui berries. The composition may comprise Fitzroya cupressoide. The flower essences may be from the traditional Bach method in which flowers are floated in a crystal bowl and left in sunlight for up to 2-3 hours, mixing with an equal volume of alcohol or red shiso. Example formulations comprising orchid (Orchidaceae) essences are given. Phytolaits may be used to form a base cream. The composition may be a topical cream, and may be a body oil.
BACKGROUND: While dyslipidemia has been recognized as a potential risk factor for hyperuricemia, there is currently a dearth of large-scale data specifically focused on studying the relationship between these two conditions. To address this gap, the present study analyzed a dataset of 298,891 physical examination records to investigate in greater detail the clinical classification and compositional relationship between hyperuricemia and dyslipidemia.
METHODS: For this investigation, a cross-sectional research design was utilized to analyze physical examination data that was gathered from Yijishan Hospital in Wuhu, China between 2011 and 2016. Logistic regression was employed to examine the association between hyperuricemia and dyslipidemia. Furthermore, the association between hyperuricemia and dyslipidemia was evaluated based on the clinical classifications of dyslipidemia and its components.
RESULTS: A total of 298,891 participants from China (124,886 [41.8%] females) were included in the study, with an age range of 18 to 90 years (mean [SD]: 47.76 [13.54] years). In multivariate analysis, the odds of hyperuricemia was 1.878 times higher in patients with dyslipidemia compared to those without dyslipidemia (95% confidence interval [CI]: 1.835-1.922). In the clinical classification of dyslipidemia, individuals with hypertriglyceridemia and mixed hyperlipidemia had 1.753 times (95% CI: 1.706-1.802) and 1.925 times (95% CI: 1.870-1.982) higher odds of hyperuricemia, respectively, compared to those without dyslipidemia. Among the components of dyslipidemia, the odds ratios for hyperuricemia in individuals in the fourth quartile compared to those in the first quartile were 3.744 (95% CI: 3.636-3.918) for triglycerides, 1.518 (95% CI: 1.471-1.565) for total cholesterol, and 1.775 (95% CI: 1.718 - 1.833) for non-high-density lipoprotein cholesterol.
CONCLUSIONS: Dyslipidemia has been independently linked with hyperuricemia. Moreover, the elevation of triglycerides or total cholesterol levels, including conditions such as hypertriglyceridemia and mixed hyperlipidemia, have been observed to have a positive association with the development of hyperuricemia.