A Student-Led Health Education Initiative Addressing Health Disparities in a Chinatown Community

Together with community advocates, professional student organizations can help improve access to health care and sustain services to address the health disparities of a community in need. This paper examines the health concerns of an underserved Chinese community and introduces a student-led health education initiative that fosters service learning and student leadership. The initiative was recognized by the American Association of Colleges of Pharmacy (AACP) and received the 2012-2013 Student Community Engaged Service Award.     

Force-dependent polymorphism in type IV pili reveals hidden epitopes

Through evolution, nature has produced exquisite nanometric structures, with features unrealized in the most advanced man-made devices. Type IV pili (Tfp) represent such a structure: 6-nm-wide retractable filamentous appendages found in many bacteria, including human pathogens. Whereas the structure of Neisseria gonorrhoeae Tfp has been defined by conventional structural techniques, it remains difficult to explain the wide spectrum of functions associated with Tfp. Here we uncover a previously undescribed force-induced quaternary structure of the N. gonorrhoeae Tfp. By using a combination of optical and magnetic tweezers, atomic force microscopy, and molecular combing to apply forces on purified Tfp, we demonstrate that Tfp subjected to approximately 100 pN of force will transition into a new conformation. The new structure is roughly 3 times longer and 40% narrower than the original structure. Upon release of the force, the Tfp fiber regains its original form, indicating a reversible transition. Equally important, we show that the force-induced conformation exposes hidden epitopes previously buried in the Tfp fiber. We postulate that this transition provides a means for N. gonorrhoeae to maintain attachment to its host while withstanding intermittent forces encountered in the environment. Our findings demonstrate the need to reassess our understanding of Tfp dynamics and functions. They could also explain the structural diversity of other helical polymers while presenting a unique mechanism for polymer elongation and exemplifying the extreme structural plasticity of biological polymers.     

ORIGINAL ARTICLE: Associations of the growth hormone receptor (GHR) gene polymorphisms with adiposity and IGF‐I activity in adolescents

Objective: To explore the genetic effect of the GH receptor (GHR) on obesity and related metabolic parameters in Hong Kong Chinese adolescents. Context: Obesity is a growing global epidemic. Increasing evidence suggests that the GH‐IGF‐I axis plays an important role in regulating adiposity and insulin sensitivity. Design: We examined the associations of genetic variants of GHR with serum IGF‐I and IGFBP‐3 levels as well as obesity‐related metabolic traits in Hong Kong Chinese adolescents. Patients: Nine hundred and eighty‐one randomly selected Hong Kong Chinese adolescents from 14 schools. Measurements: We genotyped 17 single nucleotide polymorphisms (SNP) at GHR and measured serum IGF‐I and IGFBP‐3 levels as well as obesity‐related metabolic traits including fasting plasma glucose, insulin and lipid levels. Results: There were significant associations between rs4410646 and the body composition (P = 0·0044) and blood pressure factor scores (P = 0·00017). Carriers of the CC genotype had lower body mass index, percentage body fat, waist and hip circumferences than AC and AA genotype carriers (P = 0·00030–0·0094). There was also association between rs7703713 and the IGF‐I activity factor score (P = 0·0033). The GA and AA carriers of rs7703713 had higher serum IGF‐I, higher serum IGFBP‐3 and higher IGF‐I/IGFBP‐3 molar ratio (P = 0·00069–0·025). Haplotype analysis did not increase the significance of associations. Conclusion: Our results support the role of GHR gene polymorphisms in modulating adiposity and IGF‐I activity in adolescents. Examination of interactions of these SNPs with lifestyle, environmental and perinatal factors may provide further insights into their long‐term effects on obesity and metabolic risks.     

Extended resection of primary lung cancer directly invading the liver

Abstract:   A 61-year-old woman presented with chest pain. Chest CT revealed a mass of 6 cm diameter in the right lower lobe. Bronchoscopic biopsy showed squamous cell carcinoma. Video-assisted thoracotomy revealed that the main tumour was directly invading the liver through the diaphragm. To alleviate local symptoms and for possible cure with adjuvant chemotherapy and radiotherapy, standard right lower lobectomy and mediastinal dissection were carried out, followed by combined resection of the diaphragm and posterior superior segmentectomy of the liver. Eleven months postoperatively, the patient was alive but had a metastatic lesion in the other lobe of the liver which reduced in size following chemotherapy.     

Clinical outcome and toxicity of radiotherapy for inferior vena cava tumor thrombus in HCC patients: A retrospective study

Hepatocellular carcinoma (HCC) involving the inferior vena cava rarely occurs, but its prognosis is extremely poor, with no established treatment to date. This study aimed to analyze the clinical outcome and toxicity of radiotherapy (RT) targeting inferior vena cava tumor thrombus (IVCTT) in HCC patients.From November 2011 to July 2020, medical record of 19 HCC patients who were treated with RT for IVCTT was retrospectively reviewed. RT was delivered using 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and stereotactic body radiation therapy. The median radiation dose was 50 Gy (range, 45–55.8 Gy) for intensity-modulated radiation therapy and three-dimensional conformal radiotherapy. Stereotactic body radiation therapy was performed in 5 patients, for a total of 32 Gy in 4 fractions.The median follow-up duration was 8.1 months (range, 3.3–26.5 months). The median overall survival was 9.4 months (range, 3.7–26.5 months), and the 1-year overall survival rate was 37.1%. Eight of 19 patients (42.1%) had extrahepatic metastasis at the start of RT. Six of 11 patients (54.5%) who did not have extrahepatic metastasis at the start of RT showed extrahepatic metastasis after RT. The major cause of death was progression of extrahepatic metastasis (11 patients, 57.9%). The overall response rate of IVCTT for RT was 84.2%, and the local control rate at the time of the last follow-up was 89.4%. After RT, the most common first progression site was the lungs (9 patients, 47.4%). Most toxicities were grade 1 to 2 gastrointestinal (26.3%) and liver enzyme elevation (68.4%). Three patients occurred pulmonary embolism after RT later than 5 months after.RT is a feasible and safe local therapy for IVCTT, with favorable tumor control and acceptable toxicity. Extrahepatic metastasis is the major progression pattern and a leading cause of death in patients treated with RT. The combination of effective systemic therapy with RT may have to be considered.     

Efficacy and safety of ixekizumab in patients with active psoriatic arthritis with and without concomitant conventional disease-modifying antirheumatic drugs: SPIRIT-P1 and SPIRIT-P2 3-year results

Clinical Rheumatology - To evaluate the three-year efficacy and safety of ixekizumab with and without concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use in...     

Clinical Significance of Substaging and HER2 Expression in Papillary Nonmuscle Invasive Urothelial Cancers of the Urinary Bladder

The study aimed to verify the prognostic utility, therapeutic application and clinical benefits of tumor substaging and HER2 status in papillary non-muscle invasive bladder cancer (NMIBC). Select NMIBC transurethral resection specimens from 141 patients were used to construct tissue microarrays for assessing the substaging, HER2 protein expression by immunohistochemistry (HER2-IHC) and gene amplification by dual-color silver in situ hybridization (HER2-SISH). Substages were identified by the differing depth of tumor invasion (pTa / pT1a / pT1b / pT1c). HER2 protein expression was semiquantitatively analyzed and grouped into negative (score 0, 1+) and positive (score 2+, 3+). Other clinicopathological variables were also investigated. For NMIBC, HER2-IHC and HER2-SISH showed positive results in 6/141 (4.3%) and 4/141 (2.8%) respectively, which correlated well with tumor substaging. In multivariate analysis, substaging, HER2-IHC, and HER2-SISH were found to be independent predictors of progression-free survival (P < 0.001, P < 0.001, P = 0.031). HER2-IHC was the sole independent predictor of recurrent free survival in NMIBC (P = 0.017). It is suggested that tumor substaging and HER2 status are independent predictive markers for tumor progression or recurrence, and thus could be included in diagnostic and therapeutic management for NMIBC.

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Human Urine-derived Stem Cells Seeded Surface Modified Composite Scaffold Grafts for Bladder Reconstruction in a Rat Model

We conducted this study to investigate the synergistic effect of human urine-derived stem cells (USCs) and surface modified composite scaffold for bladder reconstruction in a rat model. The composite scaffold (Polycaprolactone/Pluronic F127/3 wt% bladder submucosa matrix) was fabricated using an immersion precipitation method, and heparin was immobilized on the surface via covalent conjugation. Basic fibroblast growth factor (bFGF) was loaded onto the heparin-immobilized scaffold by a simple dipping method. In maximal bladder capacity and compliance analysis at 8 weeks post operation, the USCs-scaffold^heparin-bFGF group showed significant functional improvement (2.34 ± 0.25 mL and 55.09 ± 11.81 µL/cm H₂O) compared to the other groups (2.60 ± 0.23 mL and 56.14 ± 9.00 µL/cm H₂O for the control group, 1.46 ± 0.18 mL and 34.27 ± 4.42 µL/cm H₂O for the partial cystectomy group, 1.76 ± 0.22 mL and 35.62 ± 6.69 µL/cm H₂O for the scaffold group, and 1.92 ± 0.29 mL and 40.74 ± 7.88 µL/cm H₂O for the scaffold^heparin-bFGF group, respectively). In histological and immunohistochemical analysis, the USC-scaffold^heparin-bFGF group showed pronounced, well-differentiated, and organized smooth muscle bundle formation, a multi-layered and pan-cytokeratin-positive urothelium, and high condensation of submucosal area. The USCs seeded scaffold^heparin-bFGF exhibits significantly increased bladder capacity, compliance, regeneration of smooth muscle tissue, multi-layered urothelium, and condensed submucosa layers at the in vivo study.     

Validation of the NAFLD fibrosis score in a Chinese population with low prevalence of advanced fibrosis

OBJECTIVES:  Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. This study aimed to validate the NAFLD fibrosis score in the Chinese population.
METHODS:  NAFLD patients were prospectively recruited for liver biopsy and blood tests. The NAFLD fibrosis score was calculated as −1.675 + 0.037 × age (yr) + 0.094 × BMI (kg/m²) + 1.13 × impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio–0.013 × platelet (×10⁹/L)−0.66 × albumin (g/dL). Advanced fibrosis was defined as stage 3 to 4 fibrosis.
RESULTS:  One hundred sixty-two patients (age 46 ± 10 yr, male 59%) were included in the study. Advanced fibrosis was found in 18 (11%) patients. Only 11 of 128 patients with the NAFLD fibrosis score below the proposed low cutoff point (<−1.455) were under-staged, resulting in a high negative predictive value of 91%. Only two patients exceeded the proposed high cutoff point (>0.676), but neither had advanced fibrosis. If the NAFLD fibrosis score was implemented in the Chinese population, 79% of liver biopsies could be avoided.
CONCLUSIONS:  The NAFLD fibrosis score has high negative predictive value in excluding advanced fibrosis in the Chinese population, and can reduce the burden of liver biopsy in the vast majority of cases. Since there were few cases of advanced fibrosis in this cohort, this study had limited power in validating the high cutoff point.