Reducing the Gap in Knowledge and Expectations between Clinicians and People with Polycystic Ovary Syndrome or Adrenal Conditions: Simulation via Instant Messaging-Birmingham Advance: Patient and Public Involvement (SIMBA-PPI) Study.

BACKGROUND: To evaluate the efficacy of SIMBA as an educational intervention for both HCPs and people with either PCOS or adrenal conditions and to study the change in knowledge of people with PCOS or adrenal conditions about the conditions and expectations from the HCPs involved in their care following SIMBA-PPI sessions. METHODS: Two SIMBA-PPI sessions (SIMBA-PPI Polycystic ovary syndrome (SIMBA-PCOS) and SIMBA-PPI Adrenal conditions (SIMBA-Adrenal conditions)) were conducted in September 2021 and March 2022. In both sessions, HCPs interacted with moderators on patient management through WhatsApp. Patients with respective conditions underwent workshop-style learning in the same cases. SIMBA-PCOS transcripts were also translated into Brazilian Portuguese and workshops were held in both Brazilian Portuguese and English. The two groups (HCPs and patients) were then brought together to discuss exploring gaps in knowledge and expectations. The Wilcoxon Signed-Rank test compared differences in pre- and post-SIMBA self-reported confidence levels in HCPs and patients. Qualitative data from the online recordings were transcribed and analysed with inductive thematic analysis to identify gaps in knowledge and expectations from managing the cases. RESULTS: 48 HCPs and 25 patients participated in our study. When compared to pre-SIMBA confidence levels, SIMBA-PPI sessions effectively improved clinicians' confidence in managing PCOS (40.5%, p < .001) and adrenal conditions (23.0%, p < .001) post-SIMBA. Patient participants' confidence in HCPs significantly increased in the PCOS session (SIMBA-PCOS: 6.25%, p = 0.01). CONCLUSIONS: Integration of PPI into SIMBA improved HCPs' confidence in managing PCOS and adrenal conditions. SIMBA-PPI also improved patients' confidence in HCPs. Our findings suggest that participating in SIMBA-PPI sessions can reduce the gap in knowledge and expectations between patients and HCPs involved in their care.

Novel Management of Ocular Surface Inflammation in Patients With Ocular Graft-Versus-Host Disease in the Setting of Cataract Surgery.

PURPOSE: To report the outcomes of cataract surgery in patients with ocular graft-versus-host disease (oGVHD) using a novel preoperative immunomodulatory regimen in a collaborative subspecialty care setting. METHODS: Retrospective case series of patients with oGVHD who underwent cataract surgery using a novel preoperative immunomodulatory regimen in a collaborative care setting. A preoperative regimen consisting of pooled human immune globulin 1%, autologous serum 50%, and methylprednisolone 1% eye drops was prescribed. Outcome measures included visual acuity (VA), ocular surface disease index (OSDI) score, lissamine green staining, and complications with a minimum of 2 years of follow-up. RESULTS: Thirty-five eyes from 20 patients with oGVHD were studied. The mean age was 59 years (range 30-70 years). A healthy comparison group included 35 eyes from 24 patients with a mean age of 63 years (range 44-74 years). At the 2-year follow-up, the mean corneal staining score was 2.3/15, the mean OSDI score was 37.5, and the mean VA was 20/30 (logarithm of the minimal angle of resolution 0.17). The global complication rate was 2.8% at the last follow-up with no difference versus a healthy comparison group. CONCLUSIONS: A collaborative care model improving ocular surface health before cataract surgery with dry eye and cataract subspecialists can optimize outcomes in patients with oGVHD.

Milk supplementation: effect on piglets performance, feeding behavior and sows physiological condition during the lactation period

The present study aimed to investigate the effect of milk liquid and powder supplements on piglets' performance, drinking behavior, and sow back-fat thickness change during the lactation period. There were four experimental groups (n = 24), and in the control group (n = 6), the piglets were suckled from the sow. For the supplemental groups (n = 18), milk powder (MP), milk liquid by feeding trough (MLFT), and milk liquid feeding by the bucket (MLFB). Data were collected with the weight of a total of 252 piglets measured at birth, at 14 days and at weaning (28 days), respectively. Sow back-fat thickness was measured 3 days before farrowing, 14 days after farrowing and at weaning. There were significant differences in average daily weight gain between day 14 and weaning age for the MP and MLFT (P < 0.05) but not in MLFB (P > 0.05). For approaches to the feeder, there were significantly higher in MP and MLFT groups (P < 0.05). Based on the examination of sow back-fat thickness, the back-fat loss was minimal (P < 0.05) in the MP and MLFT compared to the MLFB and the control. Giving the milk supplement as powder and liquid by feeding trough has increased the piglets' average daily gain and body weight on day 14th and the weaning day. Moreover, the back-fat thickness reduction of sows in the supplemental groups is lower compared to the control group.

Prevalence of liver cirrhosis based on the metabolic health and weight criteria: Report from the Korea National Health and Nutrition Examination Survey (KNHANES) data analysis.

INTRODUCTION AND OBJECTIVES: Recent studies have proposed two distinctive types of obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO), based on various physiological factors. This study sought to explore the relationship between the metabolic obesity types and the incidence of liver cirrhosis (LC) in a large nationally-representative population. MATERIALS AND METHODS: Data on 27,629 adults with MHO or MUHO, were analyzed from the Korea National Health and Nutrition Examination Survey (KNHANES) obtained from 2015 through 2019. Four categories of metabolic health and weight (MHW) were generated for analysis: (1) MHO, (2) MUHO, (3) Metabolically unhealthy normal weight (MUHNW), and (4) Metabolically healthy normal weight (MHNW). Statistical analyzes were performed with univariate and multivariate logistic regression. RESULTS: The prevalence of LC did not show statistically significant differences among the MHW categories: 0.5% in MHO, 0.4% in MUHO, 0.2% in MHNW, and 0.3% in MUHNW. The unadjusted analysis showed a significant association between self-reported LC and MUHO, but this association was not evident in the adjusted analysis. In the adjusted analysis of the prevalence of laboratory LC, a significant association emerged in the MUHO group, followed in descending order of magnitude by the MHO and MUHNW groups. A favorable fasting blood glucose level was the only factor associated with increased prevalence of reported LC in MUHO. CONCLUSIONS: The study demonstrated a difference in the prevalence of LC between MHO and MUHO. Our study concludes that the MHO phenotype is a transient status with regard to metabolic abnormalities, and caution is necessary when evaluating MHO.

Hybridization Chain Reaction Fluorescence In Situ Hybridization (HCR-FISH) in Ambystoma mexicanum Tissue.

In situ hybridization is a standard procedure for visualizing mRNA transcripts in tissues. The recent adoption of fluorescent probes and new signal amplification methods have facilitated multiplexed RNA imaging in tissue sections and whole tissues. Here we present protocols for multiplexed hybridization chain reaction fluorescence in situ hybridization (HCR-FISH) staining, imaging, cell segmentation, and mRNA quantification in regenerating axolotl tissue sections. We also present a protocol for whole-mount staining and imaging of developing axolotl limbs.

Spontaneous osteoarthritis in dogs - clinical effects of single and multiple intra-articular injections of hyaluronic acid

Background: The treatments of osteoarthritis (OA) are commonly conservative and multimodal to relieve pain and improve movement. Intra-articular injection of hyaluronic acid (IAHA) has been studied as a treatment option for OA in dogs. IAHA helps restore the viscoelasticity of the synovial fluid and relieves the clinical symptoms of OA. However, the efficacy of IAHA in dogs is still a controversial subject. This study aims to confirm the IAHA effect in dogs with spontaneous OA and to compare the effectiveness depending on the number of injections. Materials, Methods & Results: Thirty dogs with spontaneous OA were assigned to a single injection group (n=17) and a 3-weekly injections group (n=13). Dogs weighing less than 10 kg were injected 1 mL of HA to the OA joint, and more than 10 kg dogs were injected 2 mL of HA. In the case of the 3-weekly injections group, the same amount was administered 3 times at 1-week intervals. After the injection, physical and orthopedic examinations were performed to check for complications. Radiographic OA score was evaluated before and 3 months after the injection to confirm and to evaluate the progression of OA. Clinical symptom evaluations were performed on pre-injection, 1-, 2-, and 3-months post-injection. They consisted of the clinical lameness score by veterinarians and Canine Brief Pain Inventory (CBPI) by owners. Results were compared with unpaired t-test, repeated-measures ANOVA with Tukey's or Sidak's multiple comparison test, or Wilcoxon test, with P < 0.05. Patients had a median age of 9 years (range 3 to 16 years) and a bodyweight of 4.8 kg (range 2 to 48 kg). No systemic side effects or major complications were detected during the trial period. IAHA produced temporary pain and discomfort in 6 cases. There was no change in the radiographic OA score before and 3 months after injections in both groups, and the difference between groups was not confirmed. In both groups, the clinical lameness score significantly decreased at 1, 2, 3 months after injection compared with pre-injection. The score was lower at 3 months after the injection than at 1 month. The clinical lameness score had no significant difference between the groups. Similarly, CBPI was all decreased in the single injection group and 3-weekly injections group compared to pre-injection, and the score at 3 months post-injection was lower than at 1 month. No significant differences between the groups were found in CBPI. Discussion: Most studies on the efficacy of IAHA in canine OA have been conducted using an experimental model, so studies on spontaneous canine OA are insufficient. This study confirmed that IAHA improves clinical symptoms such as pain relief and movement improvement in spontaneous OA dogs using CBPI and clinical lameness score. In order to confirm the optimal IAHA protocol, a single IAHA and 3-weekly IAHA were compared. The result shows that clinical symptoms improved in both single and 3-weekly injections groups, but no significant difference was confirmed during the 3-month study period. These findings may suggest that a single IAHA may have a similar effect to multiple IAHA, and repeated injections are unnecessary. In humans and canine OA models, it is reported that the effect of IAHA was maintained for 6 months. This study showed that the effect of IAHA was maintained for 3 months study period and that clinical symptoms improved at 3 months than at 1 month. In conclusion, these findings suggested that IAHA improves clinical symptoms in dogs with spontaneous OA, and a single IAHA showed a similar effect to 3 weekly IAHA.

Methyl anthranilate as pig repellent: effects on the feeding behavior and production performance

Preventing pigs such as wild pigs (Sus scrofa) from accessing the farm can be blocked by installing fences or repellent to make them feel reluctant to access the farm. Most wild pigs were captured to prevent crop damage and incidence of African swine fever (ASF). Still, there is a limit to capturing them due to the rapid population growth. A study was conducted using "To Nature" repellent with an active ingredient of Methyl anthranilate (MA) to assess the effectiveness of MA as a pig repellent and determine its effect on feeding behavior and production performance. A total of eight female pigs [(Landrace x Yorkshire) x Duroc] were randomly arranged and used in the experiment for five weeks. Each treatment was replicated four times, having one pig in every replication. The feeders' position with MA repellent was shifted weekly with a ratio of 0.25% and mixed with 10kg of feed. The number of approaches of pigs to the feeder was monitored daily using a full HD CCTV 5-megapixel camera. A significantly lower number of approaches, feed intake, and total time spent feeding in the feeding trough was recorded from the feeder with MA repellent mixed in the diet. Regression analysis revealed a positive relationship in the feeding behavior of pigs in the feeder mixed with MA repellent in the diet. Therefore, 0.25% MA repellent can be used as pig repellent without adverse effects on the production performance of growing pigs.

Clinical and radiological assessment of rhinomaxillary syndrome in Hansen's disease.

Background More than four million people today live with Hansen's disease, and 200,000 new cases are diagnosed every year. Lifetime effects of Hansen's disease manifest as changes to bones of the face, hands and feet, resulting in physical impairment, secondary complications and facial changes that can be detrimental to quality of life, particularly among the elderly. Aims This study aimed to perform a detailed characterization of rhinomaxillary syndrome and its clinical manifestations in older persons treated in the past for Hansen's disease. Methods This was a cross-sectional study to characterize rhinomaxillary syndrome among older persons (age 60+ years) resident at Pedro Fontes Hospital, Cariacica, Espírito Santo, Brazil. Computed tomography images were examined with three-dimensional reconstructions to assess alterations to maxillofacial bones according to criteria for radiological rhinomaxillary syndrome. Participants were examined to assess facial alterations according to criteria for clinical rhinomaxillary syndrome. Results Rhinomaxillary syndrome was investigated in 16 participants (ten females and six males), median age 70 (range 60-89) years, age at diagnosis 20 (6-43) years and time since diagnosis 46 (26-70) years. Four participants fully met radiological rhinomaxillary syndrome criteria, four partially. All participants with full radiological rhinomaxillary syndrome presented with facial changes which met criteria for clinical rhinomaxillary syndrome, including "saddle nose" (loss of nasal dorsal height and shortened length of nose, due to cartilaginous and/or bone collapse), concave middle third of the face with sunken nose, maxillary retrognathia and inverted upper lip. Limitations Clinical histories were incomplete for some participants because records were lost at the hospital over time. Conclusion Until Hansen's disease is eliminated from endemic countries, persons affected will continue to present with rhinomaxillofacial alterations caused by Mycobacterium leprae infection. Clinical protocols for assessment and long-term care need to include otorhinolaryngological evaluation, mainly to prevent secondary complications. When rhinomaxillofacial bone changes are suspected, this evaluation should be supported by computed tomography imaging, if available.

A survey of US hospitals' criteria for the allocation of remdesivir to treat COVID-19.

PURPOSE: To determine how hospitals across the United States determined allocation criteria for remdesivir, approved in May 2020 for treatment of coronavirus disease 2019 (COVID-19) through an emergency use authorization, while maintaining fair and ethical distribution when patient needs exceeded supply. METHODS: A electronic survey inquiring as to how institutions determined remdesivir allocation was developed. On June 17, 2020, an invitation with a link to the survey was posted on the Vizient Pharmacy Network Community pages and via email to the American College of Clinical Pharmacy's Infectious Disease Practice and Research Network listserver. RESULTS: 66 institutions representing 28 states responded to the survey. The results showed that 98% of surveyed institutions used a multidisciplinary team to develop remdesivir allocation criteria. A majority of those teams included clinical pharmacists (indicated by 97% of respondents), adult infectious diseases physicians (94%), and/or adult intensivists (69%). Many teams included adult hospitalists (49.2%) and/or ethicists (35.4%). Of the surveyed institutions, 59% indicated that all patients with COVID-19 were evaluated for treatment, and 50% delegated initial patient identification for potential remdesivir use to treating physicians. Prioritization of remdesivir allocation was often determined on a "first come, first served" basis (47% of respondents), according to a patient's respiratory status (28.8%) and/or clinical course (24.2%), and/or by random lottery (22.7%). Laboratory parameters (10.6%), comorbidities (4.5%), and essential worker status (4.5%) were rarely included in allocation criteria; no respondents reported consideration of socioeconomic disadvantage or use of a validated scoring system. CONCLUSION: The COVID-19 pandemic has exposed the inconsistencies of US medical centers' methods for allocating a limited pharmacotherapy resource that required rapid, fair, ethical and equitable distribution. The medical community, with citizen participation, needs to develop systems to continuously reevaluate criteria for treatment allocation as additional guidance and data emerge.

Phytochemical screening and anti-implantation activity of Asparagus africanus root extract in female Sprague-Dawley rats

Abstract Asparagus africanus Lam., Asparagaceae, is used traditionally as medicinal plant for treatment of various gastrointestinal disorders and for birth related applications. This study aimed to evaluate anti-implantation potential, screening for bioactive phytochemicals and to determine its toxicity. Thirty healthy rats were distributed into five groups (n = 6). Pregnant rats were orally administered vehicle and aqueous extract A. africanus at three different doses thrice daily for seven days. Misoprostol 300 µg/kg bw was used as positive control. All rats were laparotomized 24 h after the last dose and number of live fetuses, implantations and resorption sites were enumerated, and ovaries were harvested for histopathology. The phytochemical analysis was carried out using LC/MS. Acute toxicity was investigated, the animals were randomly grouped into five groups (n = 3); control, four different doses of aqueous extract A. africanus at a single dose treatment and rats were observed for 14 days. Prenatal study demonstrated that 300 mg/kg bw of extract and misoprostol were significantly increased the percentage of anti-implantation as compared to untreated rats. Histopathology of ovaries showed a dose dependent toxicity. LC/MS revealed the presence of steroidal saponins; asparasaponin II, sarsasapogenin, spirostans, and stigmasterol. The mean weight gain of rats treated with 2000 mg/kg bw of aqueous extract was significantly reduced (p = 0.032) compared to control group. In conclusion, the aqueous extract A. africanus has anti-implantation effect in female rats and is safe up to 2000 mg/kg bw. In addition, it contains some potential steroidal saponins, which could be used to explain its anti-implantation activity, however this finding needs further pharmacological studies to confirm the antifertility activities.

Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0.

OBJECTIVE: To determine rates of death or neurodevelopmental impairment (NDI) at 2 years corrected age (primary outcome) in children <32 weeks' gestation randomized to initial resuscitation with a fraction of inspired oxygen (FiO2) value of 0.21 or 1.0. STUDY DESIGN: Blinded assessments were conducted at 2-3 years corrected age with the Bayley Scales of Infant and Toddler Development, Third Edition or the Ages and Stages Questionnaire by intention to treat. RESULTS: Of the 290 children enrolled, 40 could not be contacted and 10 failed to attend appointments. Among the 240 children for whom outcomes at age 2 years were available, 1 child had a lethal congenital anomaly, 1 child had consent for follow-up withdrawn, and 23 children died. The primary outcome, which was available in 238 (82%) of those randomized, occurred in 47 of the 117 (40%) children assigned to initial FiO2 0.21 and in 38 of the 121 (31%) assigned to initial FiO2 1.0 (OR, 1.47; 95% CI, 0.86-2.5; P = .16). No difference in NDI was found in 215 survivors randomized to FiO2 0.21 vs 1.0 (OR, 1.26; 95% CI, 0.70-2.28; P = .11). In post hoc exploratory analyses in the whole cohort, children with a 5-minute blood oxygen saturation (SpO2) <80% were more likely to die or to have NDI (OR, 1.85; 95% CI, 1.07-3.2; P = .03). CONCLUSIONS: Initial resuscitation of infants <32 weeks' gestation with initial FiO2 0.21 had no significant effect on death or NDI compared with initial FiO2 1.0. Further evaluation of optimum initial FiO2, including SpO2 targeting, in a large randomized controlled trial is needed. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Network Registry ACTRN 12610001059055 and the National Malaysian Research Registry NMRR-07-685-957.

Corioangioma placentario gigante. Reporte de un caso / Giant placental chorioangioma. A case report

Resumen Antecedentes: El corioangioma es el tumor placentario benigno más frecuente (1%). Cuando miden más de 5 cm pueden causar complicaciones materno-fetales, por lo que es importante establecer el diagnóstico prenatal. Caso clínico: Paciente de 25 años, atendida en el Hospital Español de Beneficencia de Pachuca, con fetometría de 19.2 semanas, acorde con el ultrasonido del primer trimestre. En la evaluación del estudio de imagen se observó edema craneal; área cardiacatorácica 0.55 (anormal), compatible con cardiomegalia severa. El ultrasonido Doppler materno mostró la placenta en localización anterior y una tumoración de 7.53 x 6.74 x 6.33 cm, con zonas hiper e hipoecoicas, que protruía la superficie fetal de la placenta, arriba de la inserción del cordón umbilical. Los vasos de alimentación con diámetro máximo de 3 mm, ubicados superficialmente y cerca de la inserción del cordón. En la valoración del ultrasonido Doppler fetal: ACM-PVS: 33.5 cm/s, 1.37 MoM, anemia leve y DV IP 1.02 (> p95 anormal); en la vena umbilical del cordón se observó flujo pulsátil, pool máximo de 5.81 cc y longitud cervical de 4 cm. Mientras se integraba un equipo multidisciplinario se acordó tratamiento expectante hasta el nacimiento; debido a las repercusiones hemodinámicas el feto falleció. El estudio histopatológico confirmó el diagnóstico de corioangioma (hemangioma placentario), de 7 cm de diámetro mayor. Conclusiones: Es importante reportar los casos de corioangioma placentario, con la finalidad de contribuir al conocimiento y estimar las tasas de morbilidad y mortalidad materno-fetal.

Abstract Background: Chorioangioma is the most common benign placental tumour (1%). If these are greater than 5 cm, it can cause various maternal-fetal complications, so it is important to perform your prenatal diagnosis. Clinical case: Female patient of 25 years-old, attended at the Hospital Español de Beneficencia de Pachuca with suggestive diagnosis with fetus of 19.2 weeks, according to the ultrasound of the first trimester; in the imaging study cranial oedema was observed; cardiac-thoracic area 0.55 (abnormal), compatible with severe cardiomegaly. The maternal Doppler ultrasound showed the placenta in the anterior location and tumour of 7.53 x 6.74 x 6.33 cm, with hyperechoic and hypoechoic zones, which protruded the fetal surface of the placenta, above the insertion of the umbilical cord; the feeding vessels with a maximum diameter of 3 mm, located superficially and close to the insertion of the cord. In the evaluation of fetal Doppler ultrasound: ACM-PVS: 33.5 cm/s, 1.37 MoM, mild anaemia and DV IP 1.02 (> p95 abnormal); In the cord umbilical vein pulsatile flow was observed, maximum pool of 5.81 cc and cervical length of 4 cm. While a multidisciplinary team was formed, expectant treatment was agreed upon until birth; however, soon after, the fetus died due to hemodynamic repercussions. The histopathological study confirmed the diagnosis of chorioangioma (placental hemangioma), 7 cm in greatest diameter. Conclusions: It is important to report the cases of placental chorioangioma, with the purpose of contributing with the knowledge and estimating maternal-fetal morbidity and mortality rates.

A single institution's 26-year experience with nonfunctional pancreatic neuroendocrine tumors: a validation of current staging systems and a new prognostic nomogram.

OBJECTIVE: To validate the 2010 American Joint Committee on Cancer (AJCC) and 2006 European Neuroendocrine Tumor Society (ENETS) tumor staging systems for pancreatic neuroendocrine tumors (PanNETs) using the largest, single-institution series of surgically resected patients in the literature. BACKGROUND: The natural history and prognosis of PanNETs have been poorly defined because of the rarity and heterogeneity of these neoplasms. Currently, there are 2 main staging systems for PanNETs, which can complicate comparisons of reports in the literature and thereby hinder progress against this disease. METHODS: Univariate and multivariate analyses were conducted on the prognostic factors of survival using 326 sporadic, nonfunctional, surgically resected PanNET patients who were cared for at our institution between 1984 and 2011. Current and proposed models were tested for survival prognostication validity as measured by discrimination (Harrel's c-index, HCI) and calibration. RESULTS: Five-year overall-survival rates for AJCC stages I, II, and IV are 93% (88%-99%), 74% (65%-83%), and 56% (42%-73%), respectively, whereas ENETS stages I, II, III, and IV are 97% (92%-100%), 87% (80%-95%), 73% (63%-84%), and 56% (42%-73%), respectively. Each model has an HCI of 0.68, and they are no different in their ability to predict survival. We developed a simple prognostic tool just using grade, as measured by continuous Ki-67 labeling, sex, and binary age that has an HCI of 0.74. CONCLUSIONS: Both the AJCC and ENETS staging systems are valid and indistinguishable in their survival prognostication. A new, simpler prognostic tool can be used to predict survival and decrease interinstitutional mistakes and uncertainties regarding these neoplasms.

Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate.

The grading system for pancreatic neuroendocrine tumors (PanNETs) adopted in 2010 by the World Health Organization (WHO) mandates the use of both mitotic rate and Ki67/MIB-1 index in defining the proliferative rate and assigning the grade. In cases when these measures are not concordant for grade, it is recommended to assign the higher grade, but specific data justifying this approach do not exist. Thus, we counted mitotic figures and immunolabeled, using the Ki67 antibody, 297 WHO mitotic grade 1 and 2 PanNETs surgically resected at a single institution. We quantified the Ki67 proliferative index by marking at least 500 cells in "hot spots" and by using digital image analysis software to count each marked positive/negative cell and then compared the results with histologic features and overall survival. Of 264 WHO mitotic grade 1 PanNETs, 33% were WHO grade 2 by Ki67 proliferative index. Compared with concordant grade 1 tumors, grade-discordant tumors were more likely to have metastases to lymph node (56% vs. 34%) (P<0.01) and to distant sites (46% vs. 12%) (P<0.01). Discordant mitotic grade 1 PanNETs also showed statistically significantly more infiltrative growth patterns, perineural invasion, and small vessel invasion. Overall survival was significantly different (P<0.01), with discordant mitotic grade 1 tumors showing a median survival of 12 years compared with 16.7 years for concordant grade 1 tumors. Conversely, mitotic grade 1/Ki67 grade 2 PanNETs showed few significant differences from tumors that were mitotic grade 2 and either Ki67 grade 1 or 2. Our data demonstrate that mitotic rate and Ki67-based grades of PanNETs are often discordant, and when the Ki67 grade is greater than the mitotic grade, clinical outcomes and histopathologic features are significantly worse than concordant grade 1 tumors. Patients with discordant mitotic grade 1/Ki67 grade 2 tumors have shorter overall survival and larger tumors with more metastases and more aggressive histologic features. These data strongly suggest that Ki67 labeling be performed on all PanNETs in addition to mitotic rate determination to define more accurately tumor grade and prognosis.

Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves.

OBJECTIVE: Ficus deltoidea leaves have been used in traditional medicine in Southeast Asia to treat diabetes, inflammation, diarrhea, and infections. The present study was conducted to assess the genotoxicity and acute and subchronic toxicity of a standardized methanol extract of F. deltoidea leaves. METHODS: Sprague Dawley rats were orally treated with five different single doses of the extract and screened for signs of toxicity for two weeks after administration. In the subchronic study, three different doses of the extract were administered for 28 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological parameters were monitored during the study. Genotoxicity was assessed using the Ames test with the TA98 and TA100 Salmonella typhimurium strains. Phytochemical standardization was performed using a colorimeter and high-performance liquid chromatography. Heavy metal detection was performed using an atomic absorption spectrometer. RESULTS: The acute toxicity study showed that the LD50 of the extract was greater than 5000 mg/kg. In the subchronic toxicity study, there were no significant adverse effects on food consumption, body weight, organ weights, mortality, clinical chemistry, hematology, gross pathology, or histopathology. However, a dose-dependent increase in the serum urea level was observed. The Ames test revealed that the extract did not have any potential to induce gene mutations in S. typhimurium, either in the presence or absence of S9 activation. Phytochemical analysis of the extract revealed high contents of phenolics, flavonoids, and tannins. High-performance liquid chromatography analysis revealed high levels of vitexin and isovitexin in the extract, and the levels of heavy metals were below the toxic levels. CONCLUSION: The no-observed adverse effect level of F. deltoidea in rats was determined to be 2500 mg/kg.

Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves

OBJECTIVE: Ficus deltoidea leaves have been used in traditional medicine in Southeast Asia to treat diabetes, inflammation, diarrhea, and infections. The present study was conducted to assess the genotoxicity and acute and subchronic toxicity of a standardized methanol extract of F. deltoidea leaves. METHODS: Sprague Dawley rats were orally treated with five different single doses of the extract and screened for signs of toxicity for two weeks after administration. In the subchronic study, three different doses of the extract were administered for 28 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological parameters were monitored during the study. Genotoxicity was assessed using the Ames test with the TA98 and TA100 Salmonella typhimurium strains. Phytochemical standardization was performed using a colorimeter and high-performance liquid chromatography. Heavy metal detection was performed using an atomic absorption spectrometer. RESULTS: The acute toxicity study showed that the LD50 of the extract was greater than 5000 mg/kg. In the subchronic toxicity study, there were no significant adverse effects on food consumption, body weight, organ weights, mortality, clinical chemistry, hematology, gross pathology, or histopathology. However, a dose-dependent increase in the serum urea level was observed. The Ames test revealed that the extract did not have any potential to induce gene mutations in S. typhimurium, either in the presence or absence of S9 activation. Phytochemical analysis of the extract revealed high contents of phenolics, flavonoids, and tannins. High-performance liquid chromatography analysis revealed high levels of vitexin and isovitexin in the extract, and the levels of heavy metals were below the toxic levels. CONCLUSION: The no-observed adverse effect level ...

Relationships between maternal ethnicity, gestational age, birth weight, weight gain, and severe retinopathy of prematurity.

OBJECTIVE: To develop an algorithm that allows advanced identification of infants requiring treatment for retinopathy of prematurity (ROP). STUDY DESIGN: A retrospective observational study was performed at 2 tertiary neonatal units serving a multiethnic population in the UK, using data on 929 infants eligible for ROP screening. The relationships between study variables and the risk of developing ROP requiring treatment were analyzed using multiple logistic regression. RESULTS: After applying exclusion criteria, data from 589 infants were analyzed; of these, 57 required laser treatment. The proportion of treated infants was 5.9% of those born to black mothers, 9.39% of those born to white mothers, and 12.8% of those born to Asian mothers (P = .047). Multiple logistic regression showed that gestational age, birth weight, maternal ethnicity, and early weight gain were predictors for the development of ROP requiring treatment, with maternal ethnicity having greater predictive power compared with early weight gain. We developed an algorithm for predicting the development of ROP requiring treatment with sensitivity, specificity, and positive and negative predictive values of 100%, 65.7%, 23.8%, and 100%, respectively. CONCLUSION: Gestational age, birth weight, early weight gain, and maternal ethnicity are important predictors for the development of ROP requiring treatment. In a multiethnic population, an algorithm to predict development of ROP requiring treatment should include maternal ethnicity. If confirmed through prospective studies, this algorithm could reduce the number of opthalmologic examinations performed for ROP screening.