A diverse portfolio of marine protected areas can better advance global conservation and equity.

Marine protected areas (MPAs) are widely used for ocean conservation, yet the relative impacts of various types of MPAs are poorly understood. We estimated impacts on fish biomass from no-take and multiple-use (fished) MPAs, employing a rigorous matched counterfactual design with a global dataset of >14,000 surveys in and around 216 MPAs. Both no-take and multiple-use MPAs generated positive conservation outcomes relative to no protection (58.2% and 12.6% fish biomass increases, respectively), with smaller estimated differences between the two MPA types when controlling for additional confounding factors (8.3% increase). Relative performance depended on context and management: no-take MPAs performed better in areas of high human pressure but similar to multiple-use in remote locations. Multiple-use MPA performance was low in high-pressure areas but improved significantly with better management, producing similar outcomes to no-take MPAs when adequately staffed and appropriate use regulations were applied. For priority conservation areas where no-take restrictions are not possible or ethical, our findings show that a portfolio of well-designed and well-managed multiple-use MPAs represents a viable and potentially equitable pathway to advance local and global conservation.

Modified Radical Neck Dissection for Papillary Thyroid Carcinoma via a Combined Endoscopy Approach: The Transoral Approach and the Chest Approach.

BACKGROUND: Recently, modified radical neck dissection (MRND) for papillary thyroid carcinoma (PTC) has been performed by the transoral endoscopic approach.1 However, dissection of level II lymph nodes using only the transoral approach is highly difficult because of the inadequate axis of surgical view. Hence, we decided to combine the transoral and chest approaches to perform MRND. To the best of our knowledge, this is the first video case of MRND using the combined approach. PATIENT AND METHODS: A 35-year-old woman was diagnosed with cT1aN1bM0 right PTC (metastatic to right level III lymph nodes). The patient underwent total thyroidectomy, bilateral central neck dissection (CND), and right MRND via a combined endoscopic approach: the transoral and chest approaches. Total thyroidectomy and bilateral central neck dissection were performed via the transoral approach, similar to prior studies.2-6 The chest approach can help the surgeon to perform level II and the transoral approach was used to dissect the lymph node of levels III and IV. RESULTS: The total time for total thyroidectomy, bilateral CND, and right MRND was 190 min. The time for MRND was 90 min. The number of harvested lymph nodes were 14 in the right lateral compartments, and the number of metastatic lymph nodes were 2 in the lateral compartments. There were no major postoperative complications. The patient was completely satisfied with the cosmetic result. CONCLUSIONS: The combined approach of the transoral and chest approaches was sufficient to perform total thyroidectomy and MRND for levels II, III, and IV.

Transoral endoscopic thyroidectomy vestibular approach versus conventional open thyroidectomy for the treatment of benign thyroid tumours: A prospective cohort study.

INTRODUCTION: Thyroid tumours are a common condition and open surgery is a conventional method for treating benign thyroid tumours when surgery is indicated. In this study, we evaluate the outcomes of benign thyroid tumour treatment using transoral endoscopic thyroidectomy via vestibular approach (TOETVA) and compare the results with those of conventional open thyroidectomy (COT). PATIENTS AND METHODS: We conducted a prospective cohort study between 100 patients who underwent TOETVA and 100 who underwent COT surgery for benign diseases from June 2018 to December 2021 in our hospital. Outcomes between the two groups, including post-operative complications, operative time and length of stay, were compared. RESULTS: The surgical time in the TOETVA group was significantly longer than in the COT group. The operative time of lobectomy in the TOETVA and COT groups was 77.5 ± 13.3 and 51.5 ± 4.2 min, respectively, with a P < 0.001. The operative time of total thyroidectomy in the TOETVA and COT groups was 108.1 ± 7.0 and 65.0 ± 4.1 min, respectively, with a P < 0.001. There was no difference in post-operative length of stay between the two groups. In TOETVA group, there were no patients who converted to open surgery. Amongst all 200 patients in the study, there were no cases of post-operative bleeding. The transient hypoparathyroidism rate after surgery in the TOETVA and COT groups was 3% and 2%, respectively, with no statistically significant difference (P = 0.651). Similarly, the transient recurrent laryngeal nerve injury rate showed no difference between the two groups, with rates of 5% and 4% in the TOETVA and COT groups, respectively (P = 0.733). There were no cases of post-operative infection in either group in our study. At 3 months postoperatively, the cosmetic satisfaction were significantly higher in the endoscopic groups than in the conventional group (P < 0.001). CONCLUSIONS: TOETVA is a safe and effective method, with a low complication rate and optimal aesthetic results compared to traditional surgery to treat benign thyroid tumours.

Three-Port Transoral Robotic Thyroidectomy in Papillary Thyroid Carcinoma.

BACKGROUND: Although transoral thyroidectomy has become popular in thyroid surgery, transoral robotic thyroidectomy (TORT) has only been successfully applied in a very small number of medical centers worldwide.[1,2,3,4,5] In this video, we show a three-port TORT without an axillary incision for papillary thyroid carcinoma. PATIENT AND METHODS: A 35-year-old female with cT1aN0M0 papillary thyroid carcinoma had a strong motivation to proceed with surgery but avoid external neck incisions. Thus, we decided to perform a hemithyroidectomy with isthmusectomy using a transoral robotic approach, employing the da Vinci Xi surgical system. RESULTS: The operation was completed successfully without conversion to open surgery. The working space creation time, docking time, and console time were 30 min, 40 min, and 130 min, respectively. The pathological results were papillary thyroid carcinoma with 6- and 5-mm tumors. The patient was discharged 4 days after surgery without any complications such as bleeding, infection, mental nerve damage, permanent hoarseness, or hypoparathyroidism. The patient was completely satisfied with the cosmetic result. CONCLUSION: Three-port TORT without an axillary incision is a promising approach with optimal cosmetic outcomes. For Vietnam, a developing country, success in the application of TORT using the new da Vinci Xi robotic platform for thyroid cancer is an important milestone in the development of thyroid surgery.

Lipid kinase PIP5Kα contributes to Hippo pathway activation via interaction with Merlin and by mediating plasma membrane targeting of LATS1.

BACKGROUND: The Hippo pathway plays a critical role in controlled cell proliferation. The tumor suppressor Merlin and large tumor suppressor kinase 1 (LATS1) mediate activation of Hippo pathway, consequently inhibiting the primary effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid present in the plasma membrane (PM), binds to and activates Merlin. Phosphatidylinositol 4-phosphate 5-kinase α (PIP5Kα) is an enzyme responsible for PIP2 production. However, the functional role of PIP5Kα in regulation of Merlin and LATS1 under Hippo signaling conditions remains unclear. METHODS: PIP5Kα, Merlin, or LATS1 knockout or knockdown cells and transfected cells with them were used. LATS1, YAP, and TAZ activities were measured using biochemical methods and PIP2 levels were evaluated using cell imaging. Low/high cell density and serum starvation/stimulation conditions were tested. Colocalization of PIP5Kα and PIP2 with Merlin and LATS1, and their protein interactions were examined using transfection, confocal imaging, immunoprecipitation, western blotting, and/or pull-down experiments. Colony formation and adipocyte differentiation assays were performed. RESULTS: We found that PIP5Kα induced LATS1 activation and YAP/TAZ inhibition in a kinase activity-dependent manner. Consistent with these findings, PIP5Kα suppressed cell proliferation and enhanced adipocyte differentiation of mesenchymal stem cells. Moreover, PIP5Kα protein stability and PIP2 levels were elevated at high cell density compared with those at low cell density, and both PIP2 and YAP phosphorylation levels initially declined, then recovered upon serum stimulation. Under these conditions, YAP/TAZ activity was aberrantly regulated by PIP5Kα deficiency. Mechanistically, either Merlin deficiency or LATS1 deficiency abrogated PIP5Kα-mediated YAP/TAZ inactivation. Additionally, the catalytic domain of PIP5Kα directly interacted with the band 4.1/ezrin/radixin/moesin domain of Merlin, and this interaction reinforced interaction of Merlin with LATS1. In accordance with these findings, PIP5Kα and PIP2 colocalized with Merlin and LATS1 in the PM. In PIP5Kα-deficient cells, Merlin colocalization with PIP2 was reduced, and LATS1 solubility increased. CONCLUSIONS: Collectively, our results support that PIP5Kα serves as an activator of the Hippo pathway through interaction and colocalization with Merlin, which promotes PIP2-dependent Merlin activation and induces local recruitment of LATS1 to the PIP2-rich PM and its activation, thereby negatively regulating YAP/TAZ activity. Video Abstract.

PIP5Kγ Mediates PI(4,5)P2/Merlin/LATS1 Signaling Activation and Interplays with Hsc70 in Hippo-YAP Pathway Regulation.

The type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family produces the critical lipid regulator phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the plasma membrane (PM). Here, we investigated the potential role of PIP5Kγ, a PIP5K isoform, in the Hippo pathway. The ectopic expression of PIP5Kγ87 or PIP5Kγ90, two major PIP5Kγ splice variants, activated large tumor suppressor kinase 1 (LATS1) and inhibited Yes-associated protein (YAP), whereas PIP5Kγ knockdown yielded opposite effects. The regulatory effects of PIP5Kγ were dependent on its catalytic activity and the presence of Merlin and LATS1. PIP5Kγ knockdown weakened the restoration of YAP phosphorylation upon stimulation with epidermal growth factor or lysophosphatidic acid. We further found that PIP5Kγ90 bound to the Merlin's band 4.1/ezrin/radixin/moesin (FERM) domain, forming a complex with PI(4,5)P2 and LATS1 at the PM. Notably, PIP5Kγ90, but not its kinase-deficient mutant, potentiated Merlin-LATS1 interaction and recruited LATS1 to the PM. Consistently, PIP5Kγ knockdown or inhibitor (UNC3230) enhanced colony formation in carcinoma cell lines YAP-dependently. In addition, PIP5Kγ90 interacted with heat shock cognate 71-kDa protein (Hsc70), which also contributed to Hippo pathway activation. Collectively, our results suggest that PIP5Kγ regulates the Hippo-YAP pathway by forming a functional complex with Merlin and LATS1 at the PI(4,5)P2-rich PM and via interplay with Hsc70.

Bilateral Central Neck Dissection via Transoral Approach in Papillary Thyroid Carcinoma.

BACKGROUND: The transoral endoscopic vestibular approach (TOETVA) for thyroidectomy is gaining popularity (Russell et al. in Thyroid 28(7):825-829, 2018; Le et al. in Surg Laparosc Endosc Percutan Tech 30(3):209-213, 2020; Liao et al. in Laryngoscope 130(6):1603-1608, 2020). TOETVA has been utilized successfully in performing thyroidectomy, parathyroidectomy, and neck dissection, via both endoscopic and robotic techniques (Razavi et al. in Head Neck 40(10):2246-2253, 2018; Otolaryngol Head Neck Surg 159(4):625-629, 2018; Ngo et al. in J ENT, 2020. https://doi.org/10.1177/0145561320943358 ; Ann Surg Oncol 28(5):2766, 2021). In this video, we show bilateral central neck dissection via transoral approach in papillary thyroid carcinoma. PATIENT AND METHODS: A 37-year-old female with no significant medical history was diagnosed pT3bN0M0 intraoperatively with the tumor having slightly invaded the strap muscle. Thus, we decided to perform total thyroidectomy with bilateral central neck dissection via transoral approach. METHODS: Prelaryngeal dissection: in the prelaryngeal compartment, soft tissue containing these lymph nodes was intimately associated with the pyramidal lobe. Right paratracheal dissection: fibrofatty tissue was dissected off the prevertebral fascia and the trachea with preservation of right parathyroid glands. Pretracheal lymph nodes were removed with paratracheal dissection. Left paratracheal dissection: the lymphatic tissue was then dissected off the prevertebral and esophageal musculature and the trachea after identifying the left parathyroid glands. Finally, bilateral central neck dissection was finished with preservation of the nerve and parathyroid glands. RESULTS: The operation was completed successfully without conversion to open surgery. The operative time for central neck dissection was 20 min. There were nine harvested lymph nodes in the central compartments, while there were two metastatic lymph nodes of papillary thyroid carcinoma with 3 × 3 mm maximal dimension. There were no major postoperative complications. CONCLUSION: Central neck dissection via TOETVA is a safe and feasible method in selected patients.

ß-sitosterol from Clinacanthus nutans Lindau enhances osteoblastogenic activity via upregulation of differentiation related genes and proteins.

ß-sitosterol derived from Clinacanthus nutans Lindau was tested for its in vitro osteogenic activity using MC3T3-E1 pre-osteoblasts. Our results indicated that ß-sitosterol was non-toxic to the cells cultured at a concentration <20 µg/mL. Treatment of the cells with ß-sitosterol significantly enhanced the alkaline phosphatase activity up to 210 and 204.6% at 5 and 10 µg/mL, respectively (P < .05). Similarly, the mineralization activity of the ß-sitosterol treated cells was elevated up to 134, 168, 118% at a concentration of 2.5, 5, and 10 µg/mL, respectively (P < .05). In addition, this compound up-regulated several marker genes for osteoblast differentiation, including runx2, osx and col I to 2, 2.5 and 5.6 folds at 10 µg/mL, respectively (P < .05). The expression of p38 and ERK proteins involved in the MAPK signal pathway related to mineralization and differentiation was also enhanced. Thus, the osteoblastogenic activity of ß-sitosterol was fully illustrated for the first time.

Lean management for improving hospital waiting times-Case study of a Vietnamese public/general hospital emergency department.

INTRODUCTION: Emergency departments (EDs) at public hospitals in Vietnam typically face problems with overcrowding, as well as being populated by a wide variety of illnesses, resulting in increasing dissatisfaction from patients. To alleviate these problems, we used the increasingly popular value-stream mapping (VSM) and lean strategy approaches to (1) evaluate the current patient flow in EDs; (2) identify and eliminate the non-valued-added components; and (3) modify the existing process in order to improve waiting times. METHODS: Data from a total of 742 patients who presented at the ED of 108 Military Central Hospital in Hanoi, Vietnam, were collected. A VSM was developed where improvement possibilities were identified and attempts to eliminate non-value-added activities were made. A range of issues that were considered as a resource waste were highlighted, which led to a re-design process focusing on prioritizing blood tests and ultrasound procedures. On the administrative side, various measures were considered, including streamlining communication with medical departments, using QR codes for healthcare insurance payments, and efficient management of X-ray and CT scan online results. RESULTS: By implementing a lean approach, the following reductions in delay and waiting time were incurred: (1) pre-operative test results (for patients requiring medical procedures/operations) by 33.3% (from 134.4 to 89.4 min); (2) vascular interventions by 10.4% (from 54.6 to 48.9 min); and (3) admission to other hospital departments by 49.5% (from 118.3 to 59.8 min). Additionally, prior to the implementation of the lean strategy approach, only 22.9% of patients or their proxies (family members or friends), who responded to the survey, expressed satisfaction with the ED services. This percentage increased to 76.5% following the curtailment of non-value-added activities. Through statistical inferential test analyses, it can be confidently concluded that applying lean strategy and tools can improve patient flow in public/general hospital EDs and achieve better staff coordination within the various clinical and administrative hospital departments. To the authors' knowledge, such analysis in a Vietnamese hospital's ED context has not been previously undertaken.

Transoral Endoscopic Modified Radical Neck Dissection for Papillary Thyroid Carcinoma.

BACKGROUND: Recently, transoral endoscopic thyroidectomy via the vestibular approach (TOETVA) has become popular worldwide.1-3 After controlling for the technique, the authors used the transoral endoscopic approach to modified radical neck dissection (MRND) for papillary thyroid carcinoma with clinically positive lymph nodes in the lateral compartments. To the best of their knowledge, the authors report the first case of TOETVA for MRND. PATIENT: A 27-year-old woman had a diagnosis of cT1aN1bM0 right papillary thyroid carcinoma (metastatic to a small right level 4 lymph node). Therefore, total thyroidectomy, bilateral central neck dissection, and MRND of right levels 2, 3, and 4 were performed via the transoral endoscopic approach. METHODS: Total thyroidectomy and bilateral central lymph node dissections were performed based on the three-trocar Anuwong technique.4 Then, the fourth incision was made near the sixth teeth in the right oral vestibular area for insertion of the fourth 5-mm trocar, which was used to expose the lateral lymph compartment and to perform right MRND easily. RESULTS: The operation was completed successfully without conversion to open surgery. The total operative time was 170 min, and the operating time for MRND was 55 min. The numbers of harvested lymph nodes were 7 and 8 in the central and right lateral compartments, respectively. The numbers of metastatic lymph nodes were 2 and 1 in the central and lateral compartments, respectively. No major postoperative complications occurred. CONCLUSION: Transoral endoscopic MRND of levels 2, 3, and 4 can be feasible and safe for highly selected patients.

Nano encapsulated novel compound SA-10 with therapeutic activity in both acute and chronic murine hindlimb ischemia models.

The production dysregulation of reactive oxygen species (ROS) and nitric oxide (NO) in ischemic tissues results in endothelial dysfunction, hyperinflammation and poor blood circulation. Here, we report a hybrid molecule, SA-10 with both NO donating and ROS scavenging abilities that demonstrated potent cytoprotection and tube formation activity in endothelial cells under H2O2-induced oxidative stress. SA-10 loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (SA-10 NPs) were delivered intramuscularly (IM) to two murine hindlimb ischemia models. In the acute mode ischemia/reperfusion (I/R), the muscle damage, hyperinflammation, and lung edema were significantly reduced 3 days post-dose while in the chronic ischemia model, significant improvement of blood perfusion and physical endurance was observed over 30 days (P < 0.05). Elderly patients with acute and chronic limb ischemia have limited options for surgical or endovascular interventions, so we anticipate that a product like SA-10 NPs has potential as one of the therapeutic alternatives to surgery.

Hepatic hydrothorax.

Hepatic hydrothorax is defined as a pleural effusion in patients with liver cirrhosis in the absence of cardiopulmonary disease. The estimated prevalence among patients with liver cirrhosis is approximately 5-6%. The pathophysiology involves the passage of ascitic fluid from the peritoneal cavity to the pleural space through diaphragmatic defects. The diagnosis is made from clinical presentation and confirmed by diagnostic thoracentesis with pleural fluid analysis. The initial medical management is sodium restriction and diuretics, but liver transplantation provides the only definitive therapy. For patients who are not transplant candidates and those who await organ availability, other therapeutic modalities that are to be considered include transjugular intrahepatic portosystemic shunt placement, videoassisted thoracoscopic surgery repair, pleurodesis, and vasoconstrictors (eg, octreotide and terlipressin). The primary therapeutic goals are to reduce ascitic fluid production and improve symptoms to bridge the time for liver transplantation.

Etienne-Arthur Louis Fallot and his tetralogy.

Étienne-Arthur Louis Fallot (1850-1911) is one of the most significant medical figures of the 19th century with an eponymous congenital cardiac malformation. His initial account of the four anatomical features making up his tetralogy proved remarkably significant in the progression of clinical descriptions of the lesions producing cyanotic congenital cardiac disease. Although subsequently the cause of appreciable controversy, the accuracy of his initial descriptions underscore the current diagnostic and therapeutic approach to the malformation now known uniformly as tetralogy of Fallot.

A striking new species of phytotelm-breeding tree frog (Anura: Rhacophoridae) from central Vietnam.

We describe a distinctive new species of phytotelm-breeding rhacophorid frog from central Vietnam. Gracixalus lumarius sp. nov. is distinguished from all other rhacophorids in Indochina by a combination of (1) medium body size (adult males 38.9-41.6 mm; adult female 36.3 mm), (2) dorsum brown diurnally and yellow nocturnally, (3) venter pink, (4) tympanum and supratympanic fold indistinct (5) iris dark gold with a dense, relatively uniformly distributed network of black reticulations, (6) dorsum with distinctive white conical tubercles in males, and (7) eggs deposited on wall of a phyptotelm. The new species is known from montane bamboo and montane evergreen forest in Ngoc Linh Nature Reserve in Kon Tum Province, between ~1845-2160 m elevation.

Transfer Learning for Efficient Intent Prediction in Lower-Limb Prosthetics: A Strategy for Limited Datasets.

This paper presents a transfer learning method to enhance locomotion intent prediction in novel transfemoral amputee subjects, particularly in data-sparse scenarios. Transfer learning is done with three pre-trained models trained on separate datasets: transfemoral amputees, able-bodied individuals, and a mixed dataset of both groups. Each model is subsequently fine-tuned using data from a new transfemoral amputee subject. While subject-dependent models, trained and tested using individual user data, can achieve the least error rate, they require extensive training datasets. In contrast, our transfer learning approach yields comparable error rates while requiring significantly less data. This highlights the benefit of using preexisting, pre-trained features when data is scarce. As anticipated, the performance of transfer learning improves as more data from the subject is made available. We also explore the performance of the intent prediction system under various sensor configurations. We identify that a combination of a thigh inertial measurement unit and load cell offers a practical and efficient choice for sensor setup. These findings underscore the potential of transfer learning as a powerful tool for enhancing intent prediction accuracy for new transfemoral amputee subjects, even under data-limited conditions.

Osteo-inductive effect of piezoelectric stimulation from the poly(l-lactic acid) scaffolds.

Piezoelectric biomaterials can generate piezoelectrical charges in response to mechanical activation. These generated charges can directly stimulate bone regeneration by triggering signaling pathway that is important for regulating osteogenesis of cells seeded on the materials. On the other hand, mechanical forces applied to the biomaterials play an important role in bone regeneration through the process called mechanotransduction. While mechanical force and electrical charges are both important contributing factors to bone tissue regeneration, they operate through different underlying mechanisms. The utilizations of piezoelectric biomaterials have been explored to serve as self-charged scaffolds which can promote stem cell differentiation and the formation of functional bone tissues. However, it is still not clear how mechanical activation and electrical charge act together on such a scaffold and which factors play more important role in the piezoelectric stimulation to induce osteogenesis. In our study, we found Poly(l-lactic acid) (PLLA)-based piezoelectric scaffolds with higher piezoelectric charges had a more pronounced osteoinductive effect than those with lower charges. This provided a new mechanistic insight that the observed osteoinductive effect of the piezoelectric PLLA scaffolds is likely due to the piezoelectric stimulation they provide, rather than mechanical stimulation alone. Our findings provide a crucial guide for the optimization of piezoelectric material design and usage.

Effect of Honokiol on culture time and survival of Alzheimer's disease iPSC-derived neurons.

Introduction: Patient-derived induced pluripotent stem cells (iPSCs) have been widely used as disease models to test new therapeutic strategies. Moreover, the regenerative potential of stem cells can be improved with the use of biologically active compounds. Our study was designed to explore the effect of honokiol, a small polyphenol molecule extracted from Magnolia officinalis, on the survival and culture time of iPSC-derived neurons from a sporadic Alzheimer's disease (AD) patient. This study aimed to generate iPSCs from peripheral blood mononuclear cells (PBMCs) of an AD patient using episomal plasmids with a nucleofector system and differentiate them into neurons. These iPSC-derived neurons were used to investigate the effect of honokiol extracted from M. officinalis on their survival and long-term cultures. Methods: IPSCs were generated from PBMCs of an AD patient by introducing Oct-3/4, Sox2, Klf4, L-Myc, and Lin28 using NucleofectorTM Technology. Differentiation of neurons derived from iPSCs was carried out using inducers and recognized by biomarkers. The viability of iPSC-derived neurons with the addition of honokiol extracted from the bark of M. officinalis was determined by the MTT analytical kit. Results: IPSCs were generated by reprogramming AD patient-derived PBMCs and subsequently converted into neurons. The survival and growth of iPSC-derived neurons were significantly enhanced by adding honokiol in the experiment conditions. Conclusion: AD iPSC-derived neurons had a high viability rate when cultured in the presence of honokiol. These results have shown that AD iPSC-derived neurons can be an excellent model for screening neurotrophic agents and improving the conditions for long-term cultures of human iPSC-derived neurons. Honokiol proves to be a potential candidate for cellular therapeutics against neurodegenerative disorders.