Helicobacter pylori-Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma in a Girl.

Introduction: Extranodal marginal zone lymphoma (MZL) arises in a number of epithelial tissues, including the stomach, salivary gland, lung, small bowel, thyroid, ocular adnexa, skin, and elsewhere. It has also been called low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). MALT lymphoma predominantly occurs in adults and is rare in children. Case Presentation: We report a case of MALT lymphoma involving the stomach, which is the most common subtype, in a 12-year-old girl. Initially, the patient relapsed after antibiotic therapy but achieved successful treatment subsequently through irradiation. Conclusion: Helicobacter pylori eradication therapy should be given to all patients with gastric MZL, irrespective of stage. In patients who do not respond to antibiotic therapy, treatment options such as irradiation and systemic cancer therapies should be considered, depending on the disease stage.

Diterpenoid and phenolic constituents from corn silk (Zea mays) with PTP1B inhibitory activity.

Chemical investigation of corn silk resulted in the isolation of nine secondary metabolites, including a new ent-kaurane diterpenoid, zeamaysditerpene A (1) and eight known compounds, stigmaydene A (2), stigmaydene J (3), stigmaydene L (4), stigmane D (5), demethyltorosaflavone D (6), chrysoeriol 6-C-ß-boivinopyranosyl-7-O-ß-D-glucopyranoside (7), deoxypodophyllotoxin (8), and α-peltatin glucoside (9). Their structures were elucidated using a combination of spectroscopic methods, including 1D and 2D NMR and HRESIQTOF mass spectra. The absolute configuration of 1 was deduced by applying electronic circular dichroism (ECD) calculation method. Among the isolates, only 6 displayed significant inhibition against PTP1B activity in a dose-dependent manner, with an IC50 value of 10.7 ± 0.1 µM. Furthermore, molecular docking simulation was carried out to explore the action perspective of 6 inside the enzyme PTP1B. This finding suggests that 6 might be a potential lead for the development of a new anti-diabetic agent.

Isoryanodane diterpene derivatives from Barringtonia macrocarpa.

From the MeOH residue of Barringtonia macrocarpa branches and leaves, one new isoryanodane diterpene, barringisol (1), and two new isoryanodane diterpene glucosides, barringisosides A and B (2 and 3), were obtained using various chromatographic isolations. The structural characterization was confirmed by spectroscopic methods including 1D, 2D NMR and HR-ESI-QTOF-MS. This is the first isolation of isoryanodane diterpene derivatives from Barringtonia species. Moreover, the in vitro cytotoxicity of 1-3 on three human cancer cell lines (HepG2, LNCaP and MCF7) was also accessed using SRB assays.

A Multi-Institutional Needs Assessment in the Development of a Robotic Surgery Curriculum: Perceptions From Resident and Faculty Surgeons.

BACKGROUND: The growing adoption of robotic-assisted surgery mandates residents must acquire robotic skills. No standardized curriculum for robotic surgery exists. Therefore, programs have developed their own curricula, which are often unstructured and based on resource availability. With this strategy programs may not adhere to scholarly approaches in curriculum development. We aimed to obtain a multi-institutional needs assessment to address training needs and identify integral components of a formalized robotic surgery curriculum. METHODS: A 10-question survey was distributed to general surgery residents. A separate 7-question survey was sent to robotic faculty surgeons at 3 institutions. Survey questions queried demographics, opinions regarding robotic training, proficiency definitions, and identification of procedures and instructional strategies for a curriculum. Mann- Whitney U test and Fisher's exact test were performed to compare responses amongst residents and faculty. Spearman's correlation was used to identify relationships between experience or post-graduate year (PGY) with response selection. RESULTS: Both residents and faculty believed robotic training should start in the PGY1 (55.1% vs 52%; p = 0.58). Faculty recognized robotic training to be more important compared to residents (84% vs 58.1%; p < 0.05). Both groups considered a minimum of 21 to 40 robotic cases to be sufficient exposure during training (p = 0.30). Cholecystectomy (82.4% vs 72%; p = 0.261), ventral hernia repair (89.2% vs 88%; p = 1.0), inguinal hernia repair (91.9% vs 92%; p = 1.0), and right colectomy (83.8% vs 80%; p = 0.7) were considered to be the most appropriate robotic procedures during training. Both groups concurred that bedside (91.9% vs 100%; p = 0.33) and console skills training (97.3% vs 100%; p = 1.0), small group simulation (94.6% vs 72% p = 0.005), and independent practice (87.8% vs 92% p = 0.73), were instructional strategies vital to a curriculum. Faculty considered online didactic modules (96% vs 59.5%; p < 0.05) to be more important, whereas residents favored small group experiences for fundamental skills (94.6% vs. 72%; p < 0.05) and procedure-based simulation (96% vs 64%; p < 0.05). CONCLUSIONS: Our targeted needs assessment identified requisite components of a robotics curriculum, which are feasible and accepted by both residents and faculty. Medical educators can use this as a resource to develop a formal robotics training curriculum.

23-Hydroxyursolic acid from Viburnum lutescens inhibits osteoclast differentiation in vitro and lipopolysaccharide-induced bone loss in vivo by suppressing c-Fos and NF-κB signalling.

Bone homeostasis is maintained by a combination of osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Excessive osteoclast activity is linked to several bone-related disorders, including osteoporosis and rheumatoid arthritis. Pharmacological therapy might have a number of adverse effects. Therefore, the development of natural anti-osteoclastogenic drugs with greater efficacy and fewer adverse effects is desirable. In this study, the anti-osteoclastogenic effects of 23-hydroxyursolic acid (HUA), a triterpene isolated from Viburnum lutescens, were investigated in vitro and in vivo. HUA significantly inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-induced mature osteoclast differentiation by reducing the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and F-actin ring formation. It also inhibited the expression of osteoclast-specific marker genes such OSCAR, MMP-9, TRAP, DC-STAMP, and CtsK, as well as transcription factors, c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) in response to RANKL. Mice orally administered with HUA (25 and 50 mg/kg) exhibited significant protection against bone loss and osteoclast formation induced by lipopolysaccharide (LPS). HUA suppressed RANKL-induced nuclear factor kappa B (NF-κB) activation and phosphorylation of JNK and ERK mitogen-activated protein kinases (MAPKs). These results suggest that HUA attenuates osteoclast formation in vitro and in vivo by suppressing the RANKL-mediated AP1, NF-κB, and NFATc1 pathways. Therefore, HUA may be a lead compound for the prevention or treatment of osteolytic bone disorders.

Sulfated Naphthopyrones and Anthraquinones from the Vietnamese Crinoid Comanthus delicata.

Three new sulfated naphthopyrone derivatives namely delicapyrons F-H (1-3) and two new sulfated anthraquinone derivatives namely delicaquinons A (4) and B (5), together with 6-methoxycomaparvin-5-methylether-8-O-sodium sulfate (6), 6-methoxycomaparvin-8-O-sodium sulfate (7), comaparvin-8-O-sodium sulfate (8), and 3-propyl-1,6,8-trihydroxy-9,10-anthraquinone-6-O-sodium sulfate (9) were isolated from the Vietnamese crinoid Comanthus delicata. Their chemical structures were elucidated by extensive analysis of the one dimensional (1D) and 2D-NMR, high resolution electrospray ionization quadrupole time-of-flight (HR-ESI-QTOF) mass spectra as well as calculation of optical rotation. In addition, significant cytotoxicity was observed for 6 against LNCaP (prostate cancer) cell line with IC50 value of 20.29 ± 2.43 µM, whereas moderate or weak cytotoxic effects were observed for 1-3 and 5-8 on SK-Mel-2 (melanoma) cell line and 7 and 8 against LNCaP cell line, with IC50 values ranging from 49.96 ± 1.74 to 76.92 ± 5.85 µM.

Polyhydroxylated steroid derivatives from the starfish Pentaceraster regulus.

A new polyhydroxysteroid glycoside, regulusoside D (1), and a new polyhydroxylated steroid, (24S)-cholestane-3ß,5,6ß,8,15α,24-hexol (2), together with seven known compounds were purified from the starfish Pentaceraster regulus collected near Con Co Islands, Vietnam. The structure elucidation was confirmed by extensive analysis of their NMR and HR-QTOF mass experiments. Among isolated compounds, regulusoside D (1), (24S)-cholestane-3ß,5,6ß,8,15α,24-hexol (2), granulatoside A (4), 5α-cholestane-3ß,6ß,7α,15α,16ß,26-hexol (6), 5α-cholestane-3ß,6ß,7α,8ß,15α,16ß,26-heptol (7) and 5α-cholestane-3ß,6α,8,15α,16ß,26-hexol (8) exhibited strong inhibitory effects on LPS-induced NO production in RAW264.7 cells with IC50 values of 9.13 ± 1.17, 9.19 ± 0.77, 8.63 ± 3.31, 12.61 ± 0.51, 14.83 ± 3.02 and 10.98 ± 1.22 µM, respectively.

Oleanane-type triterpene saponins from Aralia armata leaves and their cytotoxic activity.

Two new, aramatosides A and B (1 and 2), together with seven known oleanane-type triterpene saponins (3-9) were isolated from the leaves of Aralia armata. Their structures were determined by combination of HR-ESI-MS, 1 D and 2 D NMR spectral data as well as comparison with the previous literature. Compounds 6-9 exhibited cytotoxic effects towards three human cancer cell lines (HT29, A2058, and A549) with IC50 values ranging from 2.01 ± 0.17 to 18.8 ± 1.17 µM. Especially, compound 7 (narcissiflorin) showed significant cytotoxic activity against HT29 and A549 cell lines with IC50 values of 2.02 ± 1.65 and 2.01 ± 0.17 µM, respectively, which are smaller than those of positive control irinotecan hydrochloride (IC50 values of 10.3 ± 1.32 and 9.89 ± 0.19 µM).

Secondary metabolites from a peanut-associated fungus Aspergillus niger IMBC-NMTP01 with cytotoxic, anti-inflammatory, and antimicrobial activities.

Chemical investigation of a peanut-associated fungal strain Aspergillus niger IMBC-NMTP01 resulted in isolation and identification of 14 secondary metabolites, including two new, epi-aspergillusol (1) and aspernigin (3), and 12 known compounds: pyrophen (2), 2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoic acid (4), aspergillusol A (5), rubrofusarin B (6), nigerasperone A (7), fonsecin (8), TMC-256C1 (9), pyranonigrin A (10), orlandin (11), nigerasperone C (12), asperpyrone A (13), and 5-(hydroxymethyl)-2-furancarboxylic acid (14). Compounds 9, 12-14 showed cytotoxicity toward all six human cancer cell lines, including HepG2, KB, HL-60, MCF-7, SK-Mel2, and LNCaP, with IC50 values ranging from 8.4 to 84.5 µM, compounds 3-5 were cytotoxic against five cancer cell lines except HepG2, whereas 1 exhibited cytotoxicity toward HepG2, KB, and MCF-7 cells. All of the compounds, except 2 and 13, inhibited NO overproduction in LPS-induced RAW264.7 cells. In addition, all of the compounds displayed antimicrobial effects against Enterococcus faecalis, whereas 13 compounds, except 10, significantly inhibited the growth of the yeast Candida albicans.

Polyacetylene and phenolic constituents from the roots of Codonopsis javanica.

Chemical investigation of the roots of Codonopsis javanica resulted in isolation of 12 compounds, including one new polyacetylene, codojavanyol (1), one new phenolic glycoside, codobenzyloside (7), and 10 known compounds, (2E,8E)-9-(tetrahydro-2H-pyran-2-yl)nona-2,8-diene-4,6-diyl-1-ol (2), lobetyol (3), lobetyolin (4), lobetyolinin (5), cordifolioidyne B (6), benzyl-α-L-arabinopyranosyl (1-6)-ß-D-glucopyranoside (8), (Z)-8-ß-D-glucopyranosyloxycinnamic acid (9), syringin (10), syringaresinol (11), and tryptophan (12). Their structures were elucidated by 1 D and 2 D NMR and MS spectroscopic analyses in comparison with the data reported in the literature. The stereochemistry of the C-2' position of 1 was identified based on time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculation. Among the isolates, compounds 3-5 were shown to have weak cytotoxicity toward three human carcinoma cell lines, including lung (A549), liver (HepG2), and breast (MCF7), with the induction of 41.4 to 55.6% cell death at the concentration of 100 µM.

Dammarane-type triterpenoid saponins from the flower buds of Panax pseudoginseng with cytotoxic activity.

Phytochemical investigation of a methanol extract of Panax pseudoginseng flower buds resulted in the isolation of 22 dammarane-type triterpenoid saponins, including three new compounds, pseudoginsenosides A-C (1-3), and 19 known analogs. Their chemical structures were identified by the comprehensive spectroscopic methods, including 1 D and 2 D NMR and mass spectra. In addition, their cytotoxic effects toward three human carcinoma cell lines, including liver (HepG2), breast (MCF7), and lung (A549) were also evaluated.

Polyhydroxylated steroids from the Vietnamese soft coral Sarcophyton ehrenbergi.

Fourteen polyhydroxylated steroids including six new compounds, ehrensteroids A - F (1-6), were isolated from the Vietnamese soft coral Sarcophyton ehrenbergi after applying various chromatographic separations. The structure elucidation was done by detailed analysis of 1D, 2D NMR and HR QTOF mass spectra. In addition, significant cytotoxicity (IC50 values ranging from 8.45 ± 0.56 to 38.27 ± 2.39 µM) against all five tested cancer cell lines as LU-1 (lung cancer), HepG2 (hepatoma cancer), MCF-7 (breast cancer), HL-60 (acute leukemia), and SW480 (colon adenocarcinoma) was observed for compounds 1, 2, 6-10, and 12-14, whereas this activity on LU-1 (IC50 = 21.91 ± 2.72 µM) and HepG2 (IC50 = 20.32 ± 0.03 µM) cell lines was also observed for 4.

Absence of SARS-CoV-2 antibodies in pre-pandemic plasma from children and adults in Vietnam

We tested pre-pandemic (2015-2019) plasma samples from 148 Vietnamese children, and 100 Vietnamese adults at high risk of zoonotic infections, for antibodies against SARS-CoV-2 nucleocapsid and spike proteins. None was positive, indicating no prior serological cross-reactivity with SARS-CoV-2 that might explain the low numbers of COVID-19 in Vietnam.

The Fellow's Perspective: The Impact of the COVID-19 Pandemic on Fellowship Training and Job Appointment.

BACKGROUND: Fellows have been uniquely affected by the widespread changes in educational structure, mandatory limitations in elective procedural volume, and hiring freezes during the COVID-19 global pandemic. STUDY DESIGN: A voluntary and anonymous survey was distributed to all Graduate Medical Education fellows at a tertiary medical center querying perspectives on clinical and didactic training and job placement. RESULTS: A total of 47 of 121 fellows (39%) completed the survey. The majority were in a medical (43%) or surgical specialty (34%) followed by critical care (13%) and procedure-based (11%) fellowships. Approximately 59% of surveyed fellows felt their programs were providing a virtual curriculum that would train them just as well as the in-person curriculum. Twenty-eight (60%) fellows were in their final or only year of training. Of the 25 fellows who were seeking employment, 52% have experienced difficulty in finding a job due to hiring freezes and 40% have encountered challenges with job interview cancellations and changes to virtual interview formats. CONCLUSION: Almost half of surveyed fellows reported an educational deterioration due to COVID-19 and graduating fellows seeking employment felt hindered by both the virtual interview format and widespread hiring freeze. Fellows are both unique and vulnerable as they balance the solidification of clinical training with securing employment during these tumultuous and unprecedented times.

Emerging carbapenem-resistant Klebsiella pneumoniae sequence type 16 causing multiple outbreaks in a tertiary hospital in southern Vietnam.

The emergence of carbapenem resistance in Klebsiella pneumoniae represents a major global public health concern. Nosocomial outbreaks caused by multidrug-resistant K. pneumoniae are commonly reported to result in high morbidity and mortality due to limited treatment options. Between October 2019 and January 2020, two concurrent high-mortality nosocomial outbreaks occurred in a referral hospital in Ho Chi Minh City, Vietnam. We performed genome sequencing and phylogenetic analysis of eight K. pneumoniae isolates from infected patients and two environmental isolates for outbreak investigation. We identified two outbreaks caused by two distinct lineages of the international sequence type (ST) 16 clone, which displayed extensive drug resistance, including resistance to carbapenem and colistin. Carbapenem-resistant ST16 outbreak strains clustered tightly with previously described ST16 K. pneumoniae from other hospitals in Vietnam, suggesting local persistence and transmission of this particular clone in this setting. We found environmental isolates from a hospital bed and blood pressure cuff that were genetically linked to an outbreak case cluster, confirming the potential of high-touch surfaces as sources for nosocomial spread of K. pneumoniae. Further, we found colistin resistance caused by disruption of the mgrB gene by an ISL3-like element, and carbapenem resistance mediated by a transferable IncF/blaOXA-181 plasmid carrying the ISL3-like element. Our study highlights the importance of coordinated efforts between clinical and molecular microbiologists and infection control teams to rapidly identify, investigate and contain nosocomial outbreaks. Routine surveillance with advanced sequencing technology should be implemented to strengthen hospital infection control and prevention measures.

The lasting footprint of COVID-19 on surgical education: A resident and attending perspective on the global pandemic.

BACKGROUND: The COVID-19 pandemic has impacted surgical training nationwide. Our former curricula will likely not return, and training will need to adapt, so we are able to graduate residents of the same caliber as prior to the pandemic. METHODS: A survey evaluating perceptions of changes made in surgical training was conducted on surgery residents and attendings. RESULTS: Disaster medicine training has become more relevant and 85% residents and 75% attendings agreed it should be incorporated into the curriculum. Safety of family was the most significant concern of residents. Virtual curriculum was perceived to be acceptable by 82% residents and only 22% attendings (p < 0.01). Residents (37%) were less concerned than attendings (61%) of falling behind on their overall training (p = 0.04). Both groups agreed operative skills would be adversely affected (56%vs72%; p = 0.37). CONCLUSIONS: To maintain an effective surgical curriculum, programs will need to implement new educational components to better prepare residents to become surgeons of the future.

New lupane-type and ursane-type triterpene saponins from the leaves of Trevesia palmata.

Three new triterpene saponins including two lupane-types and an ursane-type were isolated from the leaves of Trevesia palmata. Their structures were determined as 2α,3ß,23-trihydroxylup-20(29)-en-28-oic acid 3-O-α-L-arabinopyranoside (1), 2α,3ß,23-trihydroxylup-20(29)-en-28-oic acid 3-O-[α-L-arabinopyranoside]-28-O-[ß-D-glucopyranosyl] ester (2), and 2α,3ß,23-trihydroxyurs-12-en-28-oic acid 3-O-[α-L-arabinopyranoside]-28-O-[ß-D-glucopyranosyl(1→2)-ß-D-glucopyranosyl] ester (3) by analysis of their HR-ESI-MS, 1D and 2D NMR spectra. The 2α,3ß,23-trioxygenated pentacyclic triterpenes were uncommonly found in the nature. At concentration of 100 µM, compounds 1-3 inhibited NO production in LPS activated BV2 cells with inhibitory rates of 17.4 ± 1.8%, 33.1 ± 1.2%, and 11.7 ± 2.2%, respectively. But, they did not significantly inhibit yeast α-glucosidase activity.

Pregnane glycosides from Gymnema inodorum and their α-glucosidase inhibitory activity.

Two new pregnane glycosides, gyminosides A and B (1 and 2) and three known, tinctoroside B (3), tinctoroside C (4), and gymnepregoside F (5) were isolated from the leaves of Gymnema inodorum (Lour.) Decne. Their structures were elucidated by physical and chemical methods and comparing with those reported in the literature. All these compounds were evaluated for α-glucosidase assay. Compound 5 exhibited the most anti α-glucosidase activity with inhibitory percentage of 63.7 ± 3.9% at the concentration of 200 µM. Compounds 1-4 showed moderate anti α-glucosidase activity with inhibitory percentage ranging from 40.0 to 52.1%.

Cytotoxic phenolic compounds isolated from the fruits of Macaranga denticulata.

A new modified geranylated flavonoid, 3'-dehydroxy-solophenol C (1), along with 17 known compounds (2-18) were isolated from the fruits of Macaranga denticulata. Their structures were established by spectral analysis, such as mass spectrometry, 1D-NMR and 2D-NMR. The new geranylated flavonoid 1 showed a moderate cytotoxic activity against the A549 cell line with IC50 value of 16.0 µM. Compound 9 showed the highest cytotoxic activities against KB, HepG2, Lu-1 and MCF7 cell lines with IC50 values of 0.6, 0.8, 1.3 and 1.2 µM, respectively.

Bicyclic lactones from the octocoral Dendronephthya mucronata.

The MeOH extract of the Vietnamese octocoral Dendronephthya mucronata afforded four bicyclic lactones (1-4), including three new compounds namely dendronephthyones A-C (1-3), after subjecting it on various chromatographic separations. The structures of the isolated compounds were established by spectroscopic experiments including 1D, 2D NMR, CD and HR-QTOF-MS. In addition, compounds 1-4 were found to exhibit selective cytotoxicity against the HeLa human cancer cell line with IC50 values of 32.48 ± 2.15, 30.12 ± 1.86, 35.14 ± 1.57 and 14.45 ± 1.34 µM, respectively.