Piperic acid derivative as a molecular modulator to accelerate the IAPP aggregation process and alter its antimicrobial activity.

Piperic acid derivatives were found to affect the islet amyloid polypeptide (IAPP) aggregation process. Structure-activity relationship studies revealed that PAD-13 was an efficient molecular modulator to accelerate IAPP fibril formation by promoting primary and secondary nucleation and reducing its antimicrobial activity.

Enantioselective Nickel-Catalyzed Reductive anti-Arylative Annulation of Alkyne-Tethered Malononitriles to Construct Quaternary Stereocenters.

A nickel-catalyzed reductive desymmetrizing annulation of alkyne-tethered malononitriles and (hetero)aryl iodides is reported for the access of cyclohexenones containing an α-all-carbon quaternary stereocenter. The use of a nickel catalyst derived from an electron-rich phosphinooxazoline ligand combined with iron powder as a reductant is crucial to the success of this transformation.

An environmentally sensitive molecular rotor as a NIR fluorescent probe for the detection of islet amyloid polypeptide.

The deposits of human islet amyloid polypeptide (IAPP), also called amylin, in the pancreas have been postulated to be a factor of pancreatic ß-cell dysfunction and is one of the common pathological hallmarks of type II diabetes mellitus (T2DM). Therefore, it is imperative to gain an in-depth understanding of the formation of these aggregates. In this study, we demonstrate a rationally-designed strategy of an environmentally sensitive near-infrared (NIR) molecular rotor utilizing thioflavin T (ThT) as a scaffold for IAPP deposits. We extended the π delocalized system not only to improve the viscosity sensitivity but also to prolong the emission wavelength to the NIR region. A naphthalene moiety was also introduced to adjust the sensitivity of our designed probes to differentiate the binding microenvironment polarity of different targeted proteins. As a result, a novel NIR fluorogenic probe toward IAPP aggregates, namely AmySP-4-Nap-Ene, was first developed. When attached to different protein aggregates, this probe exhibited distinct fluorescence emission profiles. In a comparison with ThT, the fluorescence emission of non-ionic AmySP-4-Nap-Ene exhibits a significant difference between the presence of non-fibrillar and fibrillar IAPP and displays a higher binding affinity toward IAPP fibrils. Further, the AmySP-4-Nap-Ene can be utilized to monitor IAPP accumulating process and image fibrils both in vitro and in living cells.

Surgical outcome of benign cases with pelvic adhesions undergoing robotic total hysterectomy.

BACKGROUND: Robotic total hysterectomies have been considered contraindicated for patients with intra-abdominal adherences, but the evidence for this is not strong, and we hypothesized that the procedure can be of benefit even in these cases. In our research, we analyzed how the severity of pelvic adhesions affects robotic total hysterectomy, and by comparing different types of adhesions, we can further identify the outcomes differences in between, which may aid in future surgical decision making. METHODS: Prospective cohort study (Canadian Task Force classification II-2). All 410 patients with uterine myoma or adenomyosis undergoing robotic total hysterectomies between 2011 and 2016 using the da Vinci Si system by the same surgeon in Taipei Medical University Hospital were included in the study. RESULTS: Baseline characteristics, blood loss, docking time, operation time, time to perform uterine artery ligation (UAL), pain score, hospital stay, complication rate, and laparotomy conversion rate were analyzed between benign cases with or without pelvic adhesions undergoing robotic total hysterectomy. Furthermore, in our subgroups analysis, we have divided the patients with adhesion into different groups according to the severity of adhesion. The abdomen and pelvic cavity was divided into nine sections, and the outcomes of different adhesion condition were compared. We found that patients with adhesions had increased docking time and operation time, but other differences between groups were not statistically significant. The results of the adhesion group showed no significant increases in blood loss, intra- and postoperative complications, and length of hospital stay. Only significantly longer surgical time compared with the normal group was noted. CONCLUSION: Our results suggest that robotic total hysterectomies with UAL are effective and safe for patients with benign gynecologic conditions, and the surgical method should be considered even for patients with adhesion risks.

Comparison of Survival Outcomes between Minimally Invasive Surgery and Open Radical Hysterectomy in Early-Stage Cervical Cancer.

OBJECTIVES: To compare the survival outcomes between minimally invasive surgery (MIS) and laparotomy radical hysterectomy in patients with early-stage cervical cancer. METHODS: We conducted a retrospective study involving women who received a radical hysterectomy for cervical cancer, stage IA1 with lymphovascular invasion, IA2, IB1, IB2, or IIA from 2008 to 2016. Clinicopathologic and perioperative outcomes were compared using appropriate statistical methodologies. RESULTS: Oncologic survival outcomes were analyzed using the Kaplan-Meier method. Among the 105 cases identified, 58 (55.2%) and 47 (44.8%) women underwent MIS and open radical hysterectomy, respectively. Over a median follow-up period of 62 months, women who underwent MIS and open radical hysterectomy had a 5-year overall survival rate of 87.9% and 89.4% (p = 0.845) and a 5-year disease-free survival rate of 82.5% and 86.7% (p = 0.624), respectively. CONCLUSIONS: For early-stage cervical cancer, patients who underwent MIS radical hysterectomy had survival outcomes that were comparable to those who underwent open surgery at our institute.

Dynamic Changes and Temporal Association with Ambient Temperatures: Nonlinear Analyses of Stroke Events from a National Health Insurance Database.

BACKGROUND: The associations between ambient temperatures and stroke are still uncertain, although they have been widely studied. Furthermore, the impact of latitudes or climate zones on these associations is still controversial. The Tropic of Cancer passes through the middle of Taiwan and divides it into subtropical and tropical areas. Therefore, the Taiwan National Health Insurance Database can be used to study the influence of latitudes on the association between ambient temperature and stroke events. METHODS: In this study, we retrieved daily stroke events from 2010 to 2015 in the New Taipei and Taipei Cities (the subtropical areas) and Kaohsiung City (the tropical area) from the National Health Insurance Research Database. Overall, 70,338 and 125,163 stroke events, including ischemic stroke and intracerebral hemorrhage, in Kaohsiung City and the Taipei Area were retrieved from the database, respectively. We also collected daily mean temperatures from the Taipei and Kaohsiung weather stations during the same period. The data were decomposed by ensemble empirical mode decomposition (EEMD) into several intrinsic mode functions (IMFs). There were consistent 6-period IMFs with intervals around 360 days in most decomposed data. Spearman's rank correlation test showed moderate-to-strong correlations between the relevant IMFs of daily temperatures and events of stroke in both areas, which were higher in the northern area compared with those in the southern area. CONCLUSIONS: EEMD is a useful tool to demonstrate the regularity of stroke events and their associations with dynamic changes of the ambient temperature. Our results clearly demonstrate the temporal association between the ambient temperature and daily events of ischemic stroke and intracranial hemorrhage. It will contribute to planning a healthcare system for stroke seasonally. Further well-designed prospective studies are needed to elucidate the meaning of these associations.

Learning Curve of Robotic-assisted Hysterectomy With Pelvic Lymphadenectomy for Early Stage Endometrial Cancer: Analysis of 81 Cases.

BACKGROUND/AIM: The purpose of this study was to evaluate the learning curve of robotic hysterectomy and pelvic lymphadenectomy for early-stage endometrial carcinoma. PATIENTS AND METHODS: A retrospective chart review was performed on the first 81 surgeries performed by a single surgeon. The 81 cases were divided into three groups; 4 subgroups of 20 cases each, 3 subgroups of 27 cases each, and 2 subgroups of 40 cases each. The surgical outcomes in each group were analyzed, using operative time, estimated blood loss, and the number of lymph nodes resected. RESULTS: The median operating time, estimated blood loss, and number of pelvic lymph nodes were 147 min, 50 g and 23, respectively. The estimated blood loss improved over time significantly, when dividing by every 27 and 40 cases. No statistical significance was shown regarding operative time and the number of lymph nodes. CONCLUSION: Approximately, 30 cases were needed to gain proficiency in the surgical technique.

Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision.

Intrauterine adhesion (IUA), and its severe form Asherman syndrome (Asherman's syndrome), is a mysterious disease, often accompanied with severe clinical problems contributing to a significant impairment of reproductive function, such as menstrual disturbance (amenorrhea), infertility or recurrent pregnancy loss. Among these, its correlated infertility may be one of the most challenging problems. Although there are many etiologies for the development of IUA, uterine instrumentation is the main cause of IUA. Additionally, more complicated intrauterine surgeries can be performed by advanced technology, further increasing the risk of IUA. Strategies attempting to minimize the risk and reducing its severity are urgently needed. The current review will expand the level of our knowledge required to face the troublesome disease of IUA. It is separated into six sections, addressing the introduction of the normal cyclic endometrial repairing process and its abruption causing the formation of IUA; the etiology and prevalence of IUA; the diagnosis of IUA; the classification of IUA; the pathophysiology of IUA; and the primary prevention of IUA, including (1) delicate surgical techniques, such as the use of surgical instruments, energy systems, and pre-hysteroscopic management, (2) barrier methods, such as gels, intrauterine devices, intrauterine balloons, as well as membrane structures containing hyaluronate-carboxymethylcellulose or polyethylene oxide-sodium carboxymethylcellulose as anti-adhesive barrier.

18F-FDG PET/CT of Hepatosplenic Actinomycosis After Laparoscopic Cystojejunostomy for Pancreatic Pseudocyst.

ABSTRACT: We report the 18F-FDG PET/CT appearance of abdominal actinomycosis in a 48-year-old immunocompetent woman with a history of laparoscopic cystojejunostomy for pancreatic pseudocyst previously. 18F-FDG PET/CT demonstrated multiple hypermetabolism in the liver, spleen, cystojejunostomy anastomosis, greater omentum, and umbilical region. Actinomycosis was verified by biopsy. Hepatosplenic actinomycosis secondary to cystojejunostomy is extremely rare and easily to be misdiagnosed. PET/CT is helpful for auxiliary diagnosis, guiding biopsy, and exploring the extent of the disease.

A Fluorogenic Molecule for Probing Islet Amyloid Using Flavonoid as a Scaffold Design.

Aggregation of polypeptides and proteins is commonly associated with human and other vertebrate diseases. For example, amyloid plaques consisting of amyloid-ß proteins are frequently identified in Alzheimer's disease and islet amyloid formed by islet amyloid polypeptide (IAPP, amylin) can be found in most patients with type 2 diabetes (T2D). Although many fluorescent dyes have been developed to stain amyloid fibrils, very few examples have been designed for IAPP. In this study, a series of environmentally sensitive fluorescent probes using flavonoid as a scaffold design are rationally designed and synthesized. One of these probes, namely 3-HF-ene-4'-OMe, can bind to IAPP fibrils but not nonfibrillar IAPP by exhibiting a much stronger fluorescent enhancement at 535 nm. In addition, this probe shows better detection sensitivity to IAPP fibrils compared with that of conventionally used thioflavin-T. We demonstrate that 3-HF-ene-4'-OMe can be used to monitor the kinetics of IAPP fibril formation in vitro even in the presence an amyloid inhibitor. To test the specificity of the probe, we attempt to incubate this probe with amyloid fibrils formed from other amyloidogenic proteins. Interestingly, this probe shows different responses when mixed with these fibrils, suggesting the mode of binding of this probe on these fibrils could be different. Moreover, we show that this probe is not toxic to pancreatic mouse ß-cells. Further structural optimization based on the structure of 3-HF-ene-4'-OMe may yield a specific probe for imaging islet amyloid in the pancreas. That would improve our understanding of the relationship between islet amyloid and T2D.

Hyperreactio luteinalis mimicking malignancy during pregnancy with elevated CA-125.

OBJECTIVE: To report a case with benign bilateral ovarian tumor during pregnancy mimicking malignancy. CASE REPORT: A 32-year-old women at 20 weeks gestation with large bilateral adnexal masses found on prenatal ultrasound. The cysts had been growing gradually over the course of the pregnancy. MRI show huge multiple cysts in both ovaries. CA-125 was elevated at 260 U/mL. Due to initial impression was malignancy, an excisional surgery was done. Pathology revealed multiple luteinized granulosa cells with benign nature. CONCLUSION: Hyperreactio luteinalis (HL) is often asymptomatic and discovered incidentally on ultrasound or at the time of cesarean section. As the lesions are self-resolving, management is conservative and surgical intervention is required only in cases with severe complications. HL can be mistaken for malignancy, especially in cases in which the tumor marker CA-125 is elevated, leading to inadvertent surgery.

Radical Hysterectomy After Neoadjuvant Chemotherapy for Locally Bulky-Size Cervical Cancer: A Retrospective Comparative Analysis between the Robotic and Abdominal Approaches.

Radical hysterectomy (RH) is the standard treatment for early stage cervical cancer, but the surgical approach for locally bulky-size cervical cancer (LBS-CC) is still unclear. We retrospectively compared the outcomes of women with LBS-CC treated with neoadjuvant chemotherapy (NACT) and subsequent RH between the robotic (R-RH) and abdominal approaches (A-RH). Between 2012 and 2014, 39 women with LBS-CC FIGO (International Federation of Gynecology and Obstetrics) stage IB2-IIB were treated with NACT-R-RH (n = 18) or NACT-A-RH (n = 21). Surgical parameters and prognosis were compared. Patient characteristics were not significantly different between the groups, but the NACT-R-RH group had significantly more patients with FIGO stage IIB disease, received multi-agent-based NACT, and had a lower percentage of deep stromal invasion than the NACT-A-RH group. After NACT-R-RH, surgical parameters were better, but survival outcomes, such as disease-free survival (DFS) and overall survival (OS), were significantly worse. On multivariate analysis, FIGO stage IIB contributed to worse DFS (p = 0.003) and worse OS (p = 0.012) in the NACT-A-RH group. Women with LBS-CC treated with NACT-R-RH have better perioperative outcomes but poorer survival outcomes compared with those treated with NACT-A-RH. Thus, patients with FIGO stage IIB LBS-CC disease might not be suitable for surgery after multi-agent-based NACT.

Impact of uterine weight on robotic hysterectomy: Analysis of 500 cases in a single institute.

BACKGROUNDS: Robotic surgeries have been used frequently for benign diseases in gynecology. However, the advantage of robotic surgery for huge uterus is unclear. METHODS: We analyzed surgical outcomes of 527 patients who underwent robotic hysterectomies for benign diseases, separating uterine sizes into five groups by every 250 g. RESULTS: Median operative time in the five groups was 123 minutes (<250 g), 130 minutes (250-500 g), 144 minutes (500-750 g), 180 minutes (750-1000 g), and 170 minutes (>1000 g). Median estimated blood loss was 50, 100, 100, 200, and 400 mL in the five groups, respectively. The incidence of intraoperative complications did not correlate with uterine weight. CONCLUSIONS: Operative time, estimated blood loss, and the incidence of conversion to laparotomy increased with uterine size during robotic hysterectomies, especially evident in a uterus >750 g.

Allergy-like reactions to methylene blue following laparoscopic chromopertubation: A systematic review of the literature.

Methylene blue is commonly used as a tracer in sentinel lymph node mapping for many malignant diseases or chromopertubation during gynecologic laparoscopy. In contrast with other blue dyes such as patent blue V or isosulfan blue, methylene blue rarely causes an allergy-like reaction in patients undergoing sentinel lymph node mapping. However, in chromopertubation, some cases of allergy-like reaction to methylene blue have been reported; these comprise two types: an allergic reaction and methemoglobinemia. In this study, a systematic literature review of allergy-like reactions caused by methylene blue dye following laparoscopic chromopertubation was conducted. A search was conducted in PUBMED, Web of Science, and Scopus from inception until June 2018, using the terms: "methylene blue", "complication", "allergic", "hypersensitive", "lung/pulmonary edema"," methemoglobinemia", "anaphylactic shock", "chromopertubation", "pertubation", "laparoscopic", and "laparoscopy". Ultimately, the eligibility criteria were fulfilled by only 12 case reports. Among 13 cases including our case of severe anaphylactic shock after chromopertubation, allergic reactions were diagnosed in four cases, methemoglobinemia in six, and there was no confirmed diagnosis in three cases; the clinical course consisted of skin changes, blue discoloration of body fluids, respiratory failure, and hemodynamic failure, regardless of the underlying diagnoses. Regarding diagnosis, methemoglobinemia was confirmed with co-oximetry (spectrophotometry). First-line therapy included supportive care for both cases of allergic reactions and methemoglobinemia.

Primary peritoneal carcinosarcoma: A report of two cases.

OBJECTIVE: Carcinosarcomas also known as malignant mixed mullerian tumors (MMMTs) contain both carcinomatous and sarcomatous elements. Most MMMTs are arising from female genital tract, including ovaries, uterus and fallopian tubes. Extragenital carcinosarcomas are extremely rare, with an estimation less than 40 cases so far. CASE REPORT: We report two cases of primary peritoneal carcinosarcomas. An 81-year-old woman with pelvic peritoneal carcinosarcoma, heterologous type, was treated with incomplete surgery without further chemotherapy, and died of disease soon. The other one was a 76 year-old woman with abdominal peritoneal carcinosarcoma, homologous type. After optimal debulking surgery and subsequent 6 cycles of combination of paclitaxel and carboplatin chemotherapy, the patient is free of tumor half of year. CONCLUSION: Active therapy, including complete cytoreduction surgery and carboplatin-paclitaxel chemotherapy might offer a chance of disease control for these unusual primary peritoneal carcinosarcomas.

Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design.

Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic "lipid-altered" tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug.

Prevalence and determinants of depression in caregivers of cancer patients: A systematic review and meta-analysis.

BACKGROUND: Aim of this study was to estimate the prevalence rate of depression in cancer patient caregivers and to identify factors affecting depression and quality of life of cancer caregivers. METHODS: Relevant research articles were retrieved after literature search in several electronic databases. Random effects meta-analyses were performed to obtain pooled estimates of the prevalence rates of depression and anxiety; their respective scores, and quality of life scores. Significant relationships between depression and factors related to depression and quality of life reported in individual studies were identified. RESULTS: Thirty studies were included. Overall, 21,149 caregivers were appraised in these studies (age 52.65 years [95% CI: 49.65, 55.65]; 31.14% [28.40, 33.89] men). The prevalence of depression and anxiety were 42.30% [33.31, 51.29] % and 46.55% [35.59, 57.52], respectively. Quality of life score, as measured with Caregiver Quality of Life-Cancer scale was 64.55 [47.44, 81.66]. Patient's condition, caregiving burden, duration of caregiving, spouse caregiver, caregiver being unemployed, caregiver with chronic disease, caregiver's sleep quality, caregiver's avoidance, financial problems, and female sex were positively associated with depression whereas overall quality of life of caregiver, pre-loss grief, caregiver's education level, caregiver's age, caregiver's sense of coherence, and caregiver's bondage with patient were negatively associated with depression in caregivers. CONCLUSION: A considerably high prevalence of depression is found in cancer patient caregivers. Several factors may affect depression and their quality of life of cancer patient caregivers.

A rare Krukenberg tumor arising from a primary adenocarcinoma of the small intestine.

OBJECTIVE: A Krukenberg tumor is a malignancy in the ovary that metastasizes from a primary site. Here, we report a very rare case of bilateral Krukenberg tumors of the ovaries arising from a primary adenocarcinoma of the small intestine in a 53-year-old Taiwanese woman. CASE REPORT: The patient presented with a 3-month history of abdominal distension and acid regurgitation. Gastroscopy and colonoscopy findings were negative. According to the preoperative image, we highly suspected that the small bowel mass was the primary tumor with metastatic tumors to bilateral ovarian masses. The diagnosis was made immediately after operation. Results from pathology and immunohistochemical report confirmed our diagnosis. CONCLUSION: The primary lesion of a Krukenberg tumor is generally too small to be detected. Thus, careful radiographic and endoscopic exploration of the digestive system is necessary to detect the primary tumor. Immunohistochemical evaluation is also useful for determining the primary site of the adenocarcinoma.

Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta-analysis.

PURPOSE: To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes. METHODS: A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation. RESULTS: Four studies including 527 patients eligible for inclusion in meta-analysis were identified. No significant difference in the number of mature oocytes or fertilized oocytes retrieved was found between groups. Clinical pregnancy rate with dual triggering was significantly higher as compared with hCG-alone triggering (pooled OR = 0.48, 95% CI 0.31-0.77, P = 0.002), but there was no significant difference in the ongoing pregnancy rate between groups. CONCLUSION: Results of meta-analysis indicate comparable or significantly improved outcomes with the use of GnRH agonists plus hCG as compared with hCG alone for triggering of final oocyte maturation.