Performance of ChatGPT on the pharmacist licensing examination in Taiwan.

BACKGROUND: ChatGPT is an artificial intelligence model trained for conversations. ChatGPT has been widely applied in general medical education and cardiology, but its application in pharmacy has been lacking. This study examined the accuracy of ChatGPT on the Taiwanese Pharmacist Licensing Examination and investigated its potential role in pharmacy education. METHODS: ChatGPT was used on the first Taiwanese Pharmacist Licensing Examination in 2023 in Mandarin and English. The questions were entered manually one by one. Graphical questions, chemical formulae, and tables were excluded. Textual questions were scored according to the number of correct answers. Chart question scores were determined by multiplying the number and the correct rate of text questions. This study was conducted from March 5 to March 10, 2023, by using ChatGPT 3.5. RESULTS: The correct rate of ChatGPT in Chinese and English questions was 54.4% and 56.9% in the first stage, and 53.8% and 67.6% in the second stage. On the Chinese test, only pharmacology and pharmacochemistry sections received passing scores. The English test scores were higher than the Chinese test scores across all subjects and were significantly higher in dispensing pharmacy and clinical pharmacy as well as therapeutics. CONCLUSION: ChatGPT 3.5 failed the Taiwanese Pharmacist Licensing Examination. Although it is not able to pass the examination, it can be improved quickly through deep learning. It reminds us that we should not only use multiple-choice questions to assess a pharmacist's ability, but also use more variety of evaluations in the future. Pharmacy education should be changed in line with the examination, and students must be able to use AI technology for self-learning. More importantly, we need to help students develop humanistic qualities and strengthen their ability to interact with patients, so that they can become warm-hearted healthcare professionals.

Prevalence, Associated Factors, and Appropriateness of Empirical Treatment of Trichomoniasis, Bacterial Vaginosis, and Vulvovaginal Candidiasis among Women with Vaginitis.

Trichomoniasis (TV), bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC) are the most common causes of vaginitis. This study investigated the prevalence of these diagnoses, their associated factors, and the appropriateness of the empirical treatment. From March 25, 2019, to June 17, 2022, 429 women with symptoms or signs of vaginitis were enrolled in a hospital in northern Taiwan with 438 episodes of vaginitis. Vaginal swabs were collected for Gram's staining, in vitro cultures for Trichomonas vaginalis, bacteria, and yeasts, and multiplex PCR assay for TV, BV, and VVC. Their empirical treatments were recorded. Factors associated with different etiologies of vaginitis were sought in multivariable logistic regression models. The prevalence of TV, BV, and VVC were 2.1%, 22.8%, and 21.7%, respectively, while coinfections of BV and VVC, TV and BV, TV and VVC, and triple infection occurred in 5.0%, 0.2%, 0.2%, and 0.7%, respectively. Multivariable analyses revealed that having multiple sexual partners was associated with TV and BV (adjusted odds ratio [aOR] 9.756 and 3.246, respectively), while menopausal women were less likely to have VVC (aOR 0.184). Moreover, dysuria was associated with TV (aOR 4.981), vaginal itch and pelvic pain with VVC (aOR 3.223 and 0.425, respectively), and discharge pH > 4.5 with BV (aOR 1.767). Other clinical symptoms and pelvic examination features had limited value for differential diagnosis. Among the 78 empirical antifungal and metronidazole prescriptions, 55.2% were ineffective or unnecessary. Our study highlights the importance to integrate appropriate diagnostic tools into the clinical care of women with vaginitis. IMPORTANCE Vaginal complaints are widespread among women and are associated with emotional, physical, and economic burdens with challenges in their diagnosis and management. In this survey, we identified that 40% of vaginitis in Taiwan was caused by either trichomoniasis, bacterial vaginosis, vulvovaginal candidiasis, or a combination of these infections. Our data suggested that typical physical findings appeared infrequently among women with these infections and their empirical treatments were frequently inappropriate. Our findings highlighted the importance of integrating proper diagnostic tools into clinical practice to improve the diagnosis and management of vaginitis, as recommended by national and international guidelines.

Potentially inappropriate medication in long-term care wards of a veteran hospital in Taiwan: Investigation using a spreadsheet-based rapid assessment tool.

BACKGROUND: Multimorbidity and polypharmacy increase in the aging population and are accompanied by the use of potentially inappropriate medications (PIMs) and adverse drug events (ADEs). This study developed a rapid assessment tool to investigate PIM use among patients in long-term care wards. METHODS: We retrospectively collected the data of patients in long-term care wards of a veteran hospital in Taiwan between July 2019 and June 2020. The patients with chronic diseases and medications were selected. The data, including gender, age, diagnosis, and medications, were deidentified. Nonchronic disease diagnosis and short-term and topical use medications were excluded. We used Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA) and the 2019 version of the Beers Criteria to establish a rapid assessment tool. The correlations between the prevalence of PIM use and age, the number of diagnoses, and the number of medications were analyzed using SPSS version 23. RESULTS: A total of 176 patients were included in this study, of which 76.7% (n = 135) were male and 23.3% (n = 41) were female. The average age of men was 82.1 years and that of women was 83.4 years. The average number of diagnoses for men was 5.5, and that for women was 7.3. The average number of medications for men was 5.8, and that for women was 6.5. The prevalence of PIM use was 59.1% (n = 104). Logistic regression revealed that the prevalence of PIM use may be associated with the number of medications ( p < 0.001; odds ratio = 1.378). Decision tree analysis revealed that patients who simultaneously used more than four medications exhibited a higher risk of PIM. CONCLUSION: PIM use is a key factor causing ADEs among older adults. Therefore, comprehensive assessment of PIM use is necessary. This study designed a rapid assessment tool to simultaneously integrate and evaluate medications. Future studies may investigate the effectiveness of the proposed assessment tool.

Protein Glycosylation as Biomarkers in Gynecologic Cancers.

Gynecologic cancers are the leading cause of death in women. Endometrial, ovarian, and cervical cancer are the three main types of gynecologic cancers. Poor prognoses and high mortality rates of advanced-stage cancer are still challenges of all three types. Diagnostic tools for early cancer detection could be the cornerstone for further cancer treatment and prevention. Glycosylation plays a vital role in cell proliferation, adhesion, motility, and angiogenesis, and is aberrantly expressed in cancer cells. Alterations of glycosylation may represent promising biomarkers with potential diagnostic and monitoring applications, as well as disease prognosis. Many glycosylated biomarkers, including glycoprotein, glycan, and enzyme, were discovered and well-studied for application in gynecologic cancers. Some of them have been developed as targets for cancer treatment. The use of certain biomarkers for diagnostics and monitoring of gynecologic cancers has clinical advantages, as it is quantitative, comparable, convenient, and inexpensive. However, one of the single markers have sufficient sensitivity for the screening of gynecologic cancers. In this review, we introduced the details of glycosylation and the current application of glycosylated biomarkers in these three cancers. Moreover, we also reviewed the different roles of each biomarker in other cancers and aimed to understand these glycosylated biomarkers comprehensively.

Vaginal birth after cesarean section: Experience from a regional hospital.

OBJECTIVE: Trial of labor after cesarean section (TOLAC) is an option for women with previous cesarean section. However, few women choose this option because of safety concerns. We evaluate the safety and risks associated with TOLAC and the success rate of vaginal birth after cesarean delivery (VBAC). MATERIAL AND METHODS: We reviewed all patients with a history of previous cesarean section that underwent elective repeat cesarean section (ERCS) or TOLAC in a regional teaching hospital from Nov, 2013 to May, 2018. Maternal basic clinical information, intrapartum management, postpartum complications, and neonatal outcomes were analyzed. RESULTS: 199 pregnant women with a history of at least one previous cesarean section were enrolled. 156 women received ERCS and 43 women (21.6%) underwent TOLAC, with 37 (86.0%) who underwent successful VBAC. The VBAC rate was 18.6%. Higher success rate was found in women with previous vaginal birth than in women without vaginal birth (100% vs. 81.8%). One case (2.3%) in the VBAC group was complicated with uterine rupture and inevitable neonatal death during second stage of labor. The uterus was repaired without maternal complications. In another case, the newborn's condition was complicated with low APGAR score (<7) at birth due to maternal chorioamnionitis. Among indications for previous cesarean section, cephalo-pelvic disproportion (CPD) was associated with TOLAC failure and uterine rupture after VBAC. CONCLUSION: VBAC is a feasible and safe option. Modes of delivery should be thoroughly discussed when considering TOLAC for women with history of previous cesarean section due to CPD, considering its association with TOLAC failure in second stage of labor.

Experience in different modes of delivery in twin pregnancy.

BACKGROUND/PURPOSE: Vaginal delivery, compared with Cesarean delivery, remains a less chosen mode of delivery for twin pregnancy. We studied the maternal and perinatal outcomes of twin pregnancy with different modes of delivery. METHODS: A retrospective study with data collected from a regional hospital, including vital twin pregnancies delivered at gestational age of 32 weeks and above. Medical charts were reviewed for prenatal conditions and postpartum outcomes. RESULTS: Ninety-eight pairs of twins were included and 44.9% were delivered via vaginal delivery. Women in the vaginal delivery group were significantly younger (32.5 ±4.3 years versus 34.8 ±4.6 years, p < 0.01), multiparous (34.1% versus 18.5%) and with more twins in vertex-vertex presentation (70.5% versus 33.3%) compared with women in the Cesarean delivery group. There were no differences between maternal postpartum complications and neonatal outcomes in both groups. The outcomes showed longer inter-twin delivery time interval (5.7 ± 5.6 versus 1.5 ± 0.9 min, p < 0.01), less estimated blood loss (198.7 ± 144.1 versus 763.2 ± 332.3 mL, p < 0.01), and shorter maternal hospital stay (3.0 ± 0.5 versus 5.7 ± 0.5 days, p< 0.01) in the vaginal delivery group. Twenty newborns had Apgar score below seven at birth. Logistic regression analysis revealed that low Apgar score was independently related to younger maternal age, maternal obstetric diseases and fetal non-vertex presentation. Gestational weeks and mode of delivery were not related to low Apgar score. CONCLUSION: With careful case selection, vaginal delivery could be safely performed in twin pregnancies with less estimated blood loss and better recovery than Cesarean delivery.

A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their Outcomes.

DNA damage response (DDR) is important for maintaining genomic integrity of the cell. Aberrant DDR pathways lead to accumulation of DNA damage, genomic instability and malignant transformations. Gene mutations have been proven to be associated with epithelial ovarian cancer, and the majority of the literature has focused on BRCA. In this study, we investigated the somatic mutation of DNA damage response genes in epithelial ovarian cancer patients using a multiple-gene panel with next-generation sequencing. In all, 69 serous, 39 endometrioid and 64 clear cell carcinoma patients were enrolled. Serous carcinoma patients (69.6%) had higher percentages of DDR gene mutations compared with patients with endometrioid (33.3%) and clear cell carcinoma (26.6%) (p < 0.001, chi-squared test). The percentages of DDR gene mutations in patients with recurrence (53.9 vs. 32.9% p = 0.006, chi-squared test) or cancer-related death (59.2 vs. 34.4% p = 0.001, chi-squared test) were higher than those without recurrence or living patients. In endometrioid carcinoma, patients with ≥2 DDR gene mutations had shorter PFS (p = 0.0035, log-rank test) and OS (p = 0.015, log-rank test) than those with one mutation or none. In clear cell carcinoma, patients with ≥2 DDR gene mutations had significantly shorter PFS (p = 0.0056, log-rank test) and OS (p = 0.0046, log-rank test) than those with 1 DDR mutation or none. In the EOC patients, somatic DDR gene mutations were associated with advanced-stage tumor recurrence and tumor-related death. Type I EOC patients with DDR mutations had an unfavorable prognosis, especially for clear cell carcinoma.

Factors Influencing the Discordancy Between Intraoperative Frozen Sections and Final Paraffin Pathologies in Ovarian Tumors.

AIM: To retrospectively investigate the pre-operative clinical factors and ultrasonographic features that influence the accuracy of the intraoperative frozen section (IFS) of ovarian tumors. PATIENTS AND METHODS: Women with ovarian tumors that underwent IFS in one tertiary medical center were recruited from January 2010 to December 2018. Demographic and clinical data of these women were retrieved from medical records in the hospital's centralized database. RESULTS: A total of 903 ovarian tumors were enrolled, including 237 (26.2%) benign, 150 (16.6%) borderline tumor, and 516 (57.2%) malignant. The overall accuracy of IFS among all specimens was 89.9%. The sensitivities of IFS in diagnosing borderline tumors (82.0%) and malignant tumors (88.2%) were lower than in diagnosing benign tumors (98.7%, p <0.001, Z-test). The specificity of diagnosing malignant tumors (99.7%) was significantly higher than that of diagnosing benign tumors (94.7%, p <0.001, Z-test). The group with discordant IFS and final paraffin pathology (FPP) had younger age (47.2 ± 14.0 vs. 51.5 ± 11.8 years, p = 0.013, Mann-Whitney U test), and higher percentage of early-stage disease (85.2% vs. 65.1%, p = 0.001, chi-square test) and mucinous (39.3% vs. 3.3%) and endometrioid histologic types (34.4% vs. 20.2%) than the concordant group (all by chi-square test). Menopause (OR 0.34, 95% CI 0.15-0.76, p = 0.009), multicystic tumor in ultrasound (OR 2.14, 95% CI 1.14-4.01, p = 0.018), and ascites existence (OR 0.33, 95% CI 0.14-0.82, p = 0.016) were factors related to the discordant IFS by multivariate analysis. CONCLUSIONS: IFS has good accuracy in the diagnosis of ovarian tumors. We recommend more frozen tissue sampling for sonographic multicystic tumors in premenopausal women to improve the accuracy of IFS.

Morpho-physiological properties and connectivity of vasoactive intestinal polypeptide-expressing interneurons in the mouse hippocampal dentate gyrus.

The hippocampus is a key brain structure for cognitive and emotional functions. Among the hippocampal subregions, the dentate gyrus (DG) is the first station that receives multimodal sensory information from the cortex. Local-circuit inhibitory GABAergic interneurons (INs) regulate the excitation-inhibition balance in the DG principal neurons (PNs) and therefore are critical for information processing. Similar to PNs, GABAergic INs also receive distinct inhibitory inputs. Among various classes of INs, vasoactive intestinal polypeptide-expressing (VIP+ ) INs preferentially target other INs in several brain regions and thereby directly modulate the GABAergic system. However, the morpho-physiological characteristics and postsynaptic targets of VIP+ INs in the DG are poorly understood. Here, we report that VIP+ INs in the mouse DG are highly heterogeneous based on their morpho-physiological characteristics. In approximately two-thirds of morphologically reconstructed cells, their axons ramify in the hilus. The remaining cells project their axons exclusively to the molecular layer (15%), to both the molecular layer and hilus (10%), or throughout the entire DG layers (8%). Generally, VIP+ INs display variable intrinsic properties and discharge patterns without clear correlation with their morphologies. Finally, VIP+ INs are recruited with a long latency in response to theta-band cortical inputs and preferentially innervate GABAergic INs over glutamatergic PNs. In summary, VIP+ INs in the DG are composed of highly diverse subpopulations and control the DG output via disinhibition.

Single-port laparoscopic hysterectomy for uteri greater than 500 grams.

OBJECTIVES: To study the operative outcomes of single-port laparoscopic hysterectomy in uteri greater than 500 g, using either laparoscopic assisted vaginal hysterectomy (LAVH) or laparoscopic supracervical hysterectomy (LSH). MATERIALS AND METHODS: 78 patients were included in a single institute by a single surgeon from March, 2013 to January, 2018. RESULTS: The median uterine weight was 686.5 g. Larger uterine weight was correlated with longer operative time and greater estimated blood loss. Two types of operations were performed: LAVH (n = 55) or LSH (n = 23). There were no differences in operative time (150.2 ± 45.1 vs. 158.6 ± 82.1, P = 0.66) and estimated blood loss (365.8 ± 298.5 vs. 356.5 ± 46.6, ml, P = 0.94) between LAVH and LSH. However, patients in LAVH had more excess blood loss (>500 mL) compared with LSH (32.7% vs. 21.7%, P = 0.42). In the later study period, the operative time was shorter and complication rates were lower. Such differences were especially significant in the LAVH group. By multiple regression analysis, operative time was independently correlated with age, body mass index, estimated blood loss and uterine weight in LAVH. The correlation between operative time and uterine weight in LSH was attenuated by estimated blood loss. Estimated blood loss was the dominant factor correlated with longer operative time in LSH. CONCLUSIONS: Both LAVH and LSH could be feasible in uteri greater than 500 g. LSH appeared to have less complication and less blood loss than LAVH. Operative time was correlated significantly with bleeding amount. Therefore, better bleeding control and surgical experience were warrants for single-port laparoscopic hysterectomy in uteri greater than 500 g.

Overview of MARCM-Related Technologies in Drosophila Neurobiological Research.

Mosaic analysis with a repressible cell marker (MARCM)-related technologies are positive genetic mosaic labeling systems that have been widely applied in studies of Drosophila brain development and neural circuit formation to identify diverse neuronal types, reconstruct neural lineages, and investigate the function of genes and molecules. Two types of MARCM-related technologies have been developed: single-colored and twin-colored. Single-colored MARCM technologies label one of two twin daughter cells in otherwise unmarked background tissues through site-specific recombination of homologous chromosomes during mitosis of progenitors. On the other hand, twin-colored genetic mosaic technologies label both twin daughter cells with two distinct colors, enabling the retrieval of useful information from both progenitor-derived cells and their subsequent clones. In this overview, we describe the principles and usage guidelines for MARCM-related technologies in order to help researchers employ these powerful genetic mosaic systems in their investigations of intricate neurobiological topics. © 2020 by John Wiley & Sons, Inc.

Investigation of Modulatory Effect of Pinolenic Acid (PNA) on Inflammatory Responses in Human THP-1 Macrophage-Like Cell and Mouse Models.

Pinolenic acid (PNA) is a rare n-6 polyunsaturated fatty acid (n-6 PUFA) originally identified in pine seeds. Previous studies demonstrated that PNA and its elongation metabolite, Δ7-eicosatrienoic acid (Δ7-ETrA), exerted an anti-inflammatory effect in cultured cells by suppressing prostaglandin E2 (PGE2) production. The objective of this study was to further examine the in vivo anti-inflammatory properties of PNA. Using human THP-1 macrophage, we first confirmed that incorporation of PNA into cellular phospholipids suppressed the production of interleukin-6 (IL-6) (by 46%), tumor necrosis factor-α (TNF-α) (by 18%), and prostaglandin E2 (PGE2) (by 87%), and the expression of type-2 cyclooxygenase (COX-2) (by 27%). Furthermore, we demonstrated that injection of PNA or Δ7-ETrA suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, as measured by ear thickness (by 15%) and biopsy weight (by up to 29%). Both PUFA also lowered proportions of infiltrated leukocytes, neutrophils, and macrophages using flow cytometric analysis. Topical application of PNA or Δ7-ETrA on mouse back skin suppressed TPA-induced pro-inflammatory mediator production, including IL-1ß, IL-6, TNF-α, and PGE2, as well as the phosphorylation of p38- and JNK-mitogen-activated protein kinase (MAPK), but not that of ERK-MAPK. That no PNA or Δ7-ETrA was detected in the ear disc after the PUFA injection suggests that their anti-inflammatory effect might not be due to fatty acid incorporation, but to modulation of cell signaling. In conclusion, PNA and Δ7-ETrA exerted the in vivo anti-inflammatory effect by suppressing mouse ear edema and dorsal skin inflammation.

A total laparoscopic treatment strategy for Amyand's hernia complicated with appendicitis: A case report.

INTRODUCTION: The presence of a vermiform appendix in an inguinal hernia sac is known as Amyand's hernia. It is even rarer with complicated appendicitis. Formerly it was treated via an open groin approach; recently there are new trends involving the use of laparoscopy for reduction and management of appendix. Conversely the role of laparoscopy in the following hernia repair was less discussed, with no standard care. We reported a case of Amyand's hernia complicated with appendix which was managed via a total laparoscopic strategy. PRESENTATION OF CASE: A 49-year-old male presented with right groin mass with progressive pain for 3 days. Physical exams revealed incarcerated right inguinal hernia. Amyand's hernia with acute appendicitis was diagnosed preoperatively via computed tomography (CT). Emergent diagnostic laparoscopy was performed. Appendix was reduced, with appendectomy justified for signs of appendicitis. An interval total extraperitoneal (TEP) hernioplasty was performed 3 month later, with no adverse events postoperatively. DISCUSSION: In virtue of previous literature, we proposed a total laparoscopic strategy for Amyand's hernia which consists of transabdominal diagnostic laparoscopy, management of appendix, and either immediate or elective laparoscopic hernioplasty, based on status of appendix. CONCLUSION: This laparoscopic treatment strategy is feasible for Amyand's hernia, with minimized risk of surgical site infection (SSI), fair recovery and cosmesis.

Double collecting system with ectopic ureterocele masquerading as an ovarian torsion.

OBJECTIVE: Ureterocele in a duplex system is rare and commonly presented with urinary tract infection at neonatal age, infant or childhood. Symptomatic ureterocele in reproductive-age is a diagnostic challenge and should be highly awarded to avoid miss-diagnosis. CASE REPORT: An adolescent girl with right ectopic ureterocele presented as acute abdomen that mimicked ovarian torsion received emergent laparoscopic surgery. Right ureterocele was identified and excised. Computed tomography later showed bilateral renal duplications with visible renal parenchyma and upper ureters. Recurrent abdominal pain with pelvic abscess occurred 10 days after surgery. Laparoscopic right partial nephrectomy of the upper moiety and resection of the residual ureterocele was performed. Cystoscopy showed absence of intravesical ureterocele and her symptoms were completely resolved after surgery. CONCLUSION: Infected ureterocele in a duplex system is a rare condition and should be kept in mind as differential diagnosis.

Juniperonic Acid Incorporation into the Phospholipids of Murine Macrophage Cells Modulates Pro-Inflammatory Mediator Production.

Juniperonic acid (JPA; Δ5,11,14,17-20:4), originally identified in certain gymnosperm seeds, is a rare n-3 polyunsaturated fatty acid (PUFA) with lipid-modulating effects on rats and anti-proliferative effects on fibroblast cell proliferation. However, little is known how JPA exerted its immunosuppressive effect. The objective of this study was to investigate whether JPA inhibited the production of inflammatory mediators through the modulation of cellular phospholipid fatty acid compositions. Using standard lipid chemistry techniques in conjunction with argentated column chromatography, high-purity JPA (> 98%) was extracted, isolated, and purified from Biota kernels. When murine RAW264.7 macrophages were incubated with increasing concentrations of JPA, amounts of cellular phospholipid total PUFA, JPA, and Δ7-docosatetraenoic acid (Δ7-DTA; elongation product of JPA) increased in a dose-dependent manner; however, the proportions of total monounsaturated fatty acid (MUFA) and arachidonic acid (AA) decreased. JPA suppressed the production of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and the expression of inducible nitric oxide synthase (iNOS) up to 21, 75, 30, and 44%, respectively. The induction of cyclooxygenase-2 (COX-2) over-expression by JPA could account for the doubling of the PGE2 level. Furthermore, JPA suppressed the expression of phosphorylated mitogen-activated protein kinases (MAPK). In a separate study using the mouse ear edema model, we demonstrated that JPA also significantly suppressed inflammation, as measured by ear thickness and biopsy weight. The anti-inflammatory properties of JPA could be due, in part, to the incorporation of JPA into cellular phospholipids with subsequent modulation of membrane-mediated MAPK signaling.

Routine Intraoperative Neuromonitoring of the Recurrent Laryngeal Nerve to Facilitate Complete Resection and Ensure Safety in Thyroid Cancer Surgery.

Routine use of intraoperative neuromonitoring (IONM) in thyroid cancer surgery is controversial. We aimed to investigate whether it improves the completeness of thyroidectomy and ensures safety. This retrospective study included 380 thyroid cancer patients who underwent thyroidectomy, by one surgeon, between July 2006 and November 2015. Patients were grouped according to the surgeon's adaptation of IONM, as follows: none (period 1; n = 92), early (period 2; n = 141), and late (period 3; n = 147). The operative time and rates of vocal cord palsy were determined. Surgical completeness was assessed by technetium-99m imaging of the thyroid remnant and serum thyroglobulin measurement before ablation. The rate of recurrent laryngeal nerve (RLN) palsy showed a decreasing trend over time. No permanent RLN palsies occurred in nerves not invaded by tumor after routine IONM was introduced. Technetium-99m uptake (periods 1-3, 0.62 vs 0.32 vs 0.20; P < 0.01) and thyroglobulin levels (periods 1 and 2, 37.93 vs 8.98 ng/mL, respectively; P = 0.034; period 3, 9.10 ng/mL) progressively decreased. The mean thyroglobulin level dropped significantly after introduction of routine IONM. We conclude that routine IONM during thyroid cancer surgery improves surgical completeness and might prevent permanent RLN palsy over time.

Broadband achromatic optical metasurface devices.

Among various flat optical devices, metasurfaces have presented their great ability in efficient manipulation of light fields and have been proposed for variety of devices with specific functionalities. However, due to the high phase dispersion of their building blocks, metasurfaces significantly suffer from large chromatic aberration. Here we propose a design principle to realize achromatic metasurface devices which successfully eliminate the chromatic aberration over a continuous wavelength region from 1200 to 1680 nm for circularly-polarized incidences in a reflection scheme. For this proof-of-concept, we demonstrate broadband achromatic metalenses (with the efficiency on the order of ∼12%) which are capable of focusing light with arbitrary wavelength at the same focal plane. A broadband achromatic gradient metasurface is also implemented, which is able to deflect wide-band light by the same angle. Through this approach, various flat achromatic devices that were previously impossible can be realized, which will allow innovation in full-color detection and imaging.Metasurfaces suffer from large chromatic aberration due to the high phase dispersion of their building blocks, limiting their applications. Here, Wang et al. design achromatic metasurface devices which eliminate the chromatic aberration over a continuous region from 1200 to 1680 nm in a reflection schleme.

Semaphorin-1a prevents Drosophila olfactory projection neuron dendrites from mis-targeting into select antennal lobe regions.

Elucidating how appropriate neurite patterns are generated in neurons of the olfactory system is crucial for comprehending the construction of the olfactory map. In the Drosophila olfactory system, projection neurons (PNs), primarily derived from four neural stem cells (called neuroblasts), populate their cell bodies surrounding to and distribute their dendrites in distinct but overlapping patterns within the primary olfactory center of the brain, the antennal lobe (AL). However, it remains unclear whether the same molecular mechanisms are employed to generate the appropriate dendritic patterns in discrete AL glomeruli among PNs produced from different neuroblasts. Here, by examining a previously explored transmembrane protein Semaphorin-1a (Sema-1a) which was proposed to globally control initial PN dendritic targeting along the dorsolateral-to-ventromedial axis of the AL, we discover a new role for Sema-1a in preventing dendrites of both uni-glomerular and poly-glomerular PNs from aberrant invasion into select AL regions and, intriguingly, this Sema-1a-deficient dendritic mis-targeting phenotype seems to associate with the origins of PNs from which they are derived. Further, ectopic expression of Sema-1a resulted in PN dendritic mis-projection from a select AL region into adjacent glomeruli, strengthening the idea that Sema-1a plays an essential role in preventing abnormal dendritic accumulation in select AL regions. Taken together, these results demonstrate that Sema-1a repulsion keeps dendrites of different types of PNs away from each other, enabling the same types of PN dendrites to be sorted into destined AL glomeruli and permitting for functional assembly of olfactory circuitry.

Cell Lineage Analyses and Gene Function Studies Using Twin-spot MARCM.

Mosaic analysis with a repressible cell marker (MARCM) is a positive mosaic labeling system that has been widely applied in Drosophila neurobiological studies to depict intricate morphologies and to manipulate the function of genes in subsets of neurons within otherwise unmarked and unperturbed organisms. Genetic mosaics generated in the MARCM system are mediated through site-specific recombination between homologous chromosomes within dividing precursor cells to produce both marked (MARCM clones) and unmarked daughter cells during mitosis. An extension of the MARCM method, called twin-spot MARCM (tsMARCM), labels both of the twin cells derived from a common progenitor with two distinct colors. This technique was developed to enable the retrieval of useful information from both hemi-lineages. By comprehensively analyzing different pairs of tsMARCM clones, the tsMARCM system permits high-resolution neural lineage mapping to reveal the exact birth-order of the labeled neurons produced from common progenitor cells. Furthermore, the tsMARCM system also extends gene function studies by permitting the phenotypic analysis of identical neurons of different animals. Here, we describe how to apply the tsMARCM system to facilitate studies of neural development in Drosophila.

Morphogenetic Studies of the Drosophila DA1 Ventral Olfactory Projection Neuron.

In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry.