Compliance with new drug use and the effect of discrepant drug susceptibility testing on MDR/RR-TB treatment.

BACKGROUND: Following the WHO???s announcement in 2018, the use of new drugs was recommended for all patients with multidrug-resistant TB (MDR-TB) in Korea. This study aimed to evaluate adherence to new anti-TB drug regimens and implementation of molecular drug susceptibility testing (mDST) in Korea.METHODS: Nationwide, 560 patients were reported as having MDR-TB in 2021. The implementation of mDST and new anti-TB drug use were analysed. The discrepancy between mDST and phenotypic DST (pDST) results and their implications on the use of new anti-TB drugs were also analysed. The use of novel anti-TB drugs has been approved by the National TB Expert Committee.RESULTS: The non-adherence rate in MDR-TB patients was 14.3%. The mDST implementation rate was 96.1%. Of the 459 patients who underwent both mDST and pDST, the discordance rate for rifampicin (RIF) resistance was 22.6% (n = 104), of which 72.1% (n = 75) were resistant on mDST but susceptible on pDST. The discrepancy in mDST and pDST results related to RIF resistance was found to be the main cause of non-adherence to new drug regimen.CONCLUSION: Comprehensive training on how to interpret conflicting results between mDST and pDST could enhance the utilisation of new drugs in the treatment of MDR/RIF-resistant TB.

Treatment outcomes of multidrug-resistant TB with selective use of new drugs.

SETTING: This was a nationwide cohort study.OBJECTIVE: To assess the treatment outcomes in patients with multidrug-resistant TB (MDR-TB) who underwent treatment guided by a national TB expert review committee in South Korea.DESIGN: We enrolled all patients with MDR-TB submitted for approval for the use of new TB drugs, including bedaquiline and delamanid, from 2016 to 2019. Patients were classified into two groups: those on new TB drugs and those not on new TB drugs. We compared the final treatment outcomes between the groups and analysed the prognostic factors.RESULTS: Of a total of 785 patients, respectively 754 (96.1%) and 31 (3.9%) were classified into the "new TB drugs" group and "no new TB drugs" group. The new TB drugs group had a higher acid-fast bacilli smear positivity rate and higher resistance rate to second-line injectable drugs or fluoroquinolones. Of all the patients, 97.8% achieved culture conversion (97.7% vs. 100%), and 80.4% achieved treatment success (80.2% vs. 86.7%); there was no difference between the two groups.CONCLUSIONS: New drugs are currently recommended for use in all MDR-TB treatment regimens, and the use of new drugs, as determined by an expert committee, in mainly quinolone-susceptible MDR-TB, did not compromise the treatment success rate.

Malignant Peripheral Nerve Sheath Tumour in the Urinary Bladder of a Dog.

A 15-year-old neutered male miniature pinscher was presented with a pedunculated mass (4 × 1 cm) in its urinary bladder. Exploratory cystotomy revealed that the mass was located at the trigone of the bladder and projected into the lumen. The cut surface of the mass was homogeneous grey to tan in colour with focal brown pigmentation. Microscopically, the mass was predominantly composed of neoplastic spindle cells characterized by moderate cellular pleomorphism, invasion into the muscular layer of the bladder wall and few mitotic figures. The neoplastic spindle cells formed interwoven bundles intersecting at various angles. Immunohistochemically, these cells were negative for cytokeratin 7 and α-smooth muscle actin, but strongly expressed S100 and vimentin, confirming a diagnosis of a malignant peripheral nerve sheath tumour (PNST). To the best of our knowledge, this is the first report of a primary malignant PNST in the urinary bladder of a dog.

Evidence for a Field-Induced Quantum Spin Liquid in α-RuCl_{3}.

We report a ^{35}Cl nuclear magnetic resonance study in the honeycomb lattice α-RuCl_{3}, a material that has been suggested to potentially realize a Kitaev quantum spin liquid (QSL) ground state. Our results provide direct evidence that α-RuCl_{3} exhibits a magnetic-field-induced QSL. For fields larger than ∼10 T, a spin gap opens up while resonance lines remain sharp, evidencing that spins are quantum disordered and locally fluctuating. The spin gap increases linearly with an increasing magnetic field, reaching ∼50 K at 15 T, and is nearly isotropic with respect to the field direction. The unusual rapid increase of the spin gap with increasing field and its isotropic nature are incompatible with conventional magnetic ordering and, in particular, exclude that the ground state is a fully polarized ferromagnet. The presence of such a field-induced gapped QSL phase has indeed been predicted in the Kitaev model.

Behaviour of human dental pulp cells cultured in a collagen hydrogel scaffold cross-linked with cinnamaldehyde.

AIM: To investigate the effects of the cross-linking agent cinnamaldehyde (CA) on differentiation of human dental pulp cells (hDPCs) cultured in a collagen hydrogel, which may be useful as a scaffold for regenerative endodontic therapy. METHODOLOGY: The odontogenic potential of hDPCs exposed to CA was examined using alkaline phosphatase (ALP) activity, Alizarin red S staining and real-time polymerase chain reaction for odontogenic gene expression. The morphological features of hDPCs cultured in CA-treated collagen were evaluated by scanning electron microscopy. Determination of cell numbers for evaluating proliferation was assessed by optical and fluorescence microscopy. To assess the mechanical properties of collagen treated with CA, setting time, compressive strength and surface roughness were measured. Statistical analysis was performed using Student's t-test compared with control (P = 0.05). RESULTS: CA per se did not increase ALP activity, calcium nodule formation and expression of odontogenic-related markers (P > 0.05). On the contrary, the proliferation and odontogenic differentiation of hDPCs cultured in a collagen scaffold was promoted in the presence of CA (P < 0.05). The setting time was significantly shortened, and the compressive strength and surface roughness were increased by treatment with CA (P < 0.05). CONCLUSIONS: Cross-linking of collagen scaffolds by CA had beneficial effects with respect to attachment, proliferation and differentiation of hDPCs. Consequently, the application of cross-linking agents such as CA may represent a new strategy for dentine-pulp complex regeneration.

Analysis of 'Fuji' apple somatic variants from next-generation sequencing.

The domesticated apple (Malus x domestica Borkh.) is a major fruit crop of temperate regions of the world. 'Fuji' apple (Ralls Genet x Delicious), a famous apple cultivar in Korea, has been very popular since its promotion in Japan in 1958. 'Fuji' and its bud mutant cultivars possess variable levels of genetic diversity. Nonetheless, the phenotypes of each group, which are classified into the bud mutation groups: early season, fruiting spur, and coloring, are similar. Despite attempts to identify these bud mutation cultivars, molecular markers, which were developed before the emergence of next-generation sequencing technology, have not been able to distinguish each cultivar easily. In this study, we adopted the resequencing technique using the 'Golden Delicious' (Grimes Golden x Unknown) apple genome as a reference. SNPs (single nucleotide polymorphisms) and InDels (insertions or deletions) of 'Fuji' apple and its bud mutant cultivar were detected and SNPs and unique InDels distinct to each cultivar were identified. Data from this study may be used to identify bud mutant cultivars of 'Fuji' apples and be useful for further breeding of apples.

The 7 × 1 Fermi Surface Reconstruction in a Two-dimensional f -electron Charge Density Wave System: PrTe3.

The electronic structure of a charge density wave (CDW) system PrTe3 and its modulated structure in the CDW phase have been investigated by employing ARPES, XAS, Pr 4 f RPES, and first-principles band structure calculation. Pr ions are found to be nearly trivalent, supporting the CDW instability in the metallic Te sheets through partial filling. Finite Pr 4 f spectral weight is observed near the Fermi level, suggesting the non-negligible Pr 4 f contribution to the CDW formation through the Pr 4 f -Te 5p hybridization. The two-fold symmetric features in the measured Fermi surface (FS) of PrTe3 are explained by the calculated FS for the assumed 7 × 1 CDW supercell formation in Te sheets. The shadow bands and the corresponding very weak FSs are observed, which originate from both the band folding due to the 3D interaction of Te sheets with neighboring Pr-Te layers and that due to the CDW-induced FS reconstruction. The straight vertical FSs are observed along kz, demonstrating the nearly 2D character for the near-EF states. The observed linear dichroism reveals the in-plane orbital character of the near-EF Te 5p states.

Ovarian large cell neuroendocrine carcinoma in the youngest woman.

Large cell neuroendocrine carcinoma (LCNC) of the ovary is a rare tumor in gynecologic oncologic field. An 18-year-old woman presented with abdominal distention and a pelvic mass measuring ten cm in diameter, who previously underwent laparoscopic ovarian cystectomy due to large borderline mucinous ovarian neoplasm 18 months prior. A debulking operation was optimally performed, which included total abdominal hysterectomy with bilateral salpingo-oophorectomy, bilateral pelvic lymph node dissection, bilateral paraaortic lymph node dissection, omentectomy, optimal debulking of gastrohepatic mass and subdiaphragmatic mass, and pelvic peritonectomy. Despite adjuvant chemotherapy with paclitaxel and carboplatin, the patient died of progressive disease seven months after surgery. The authors report the youngest case of LCNC of the ovary, that failed chemotherapy and had the previous history of the conservative surgical treatment due to mucinous borderline tumor.

Rectovaginal fistula caused by retained colpotomy cup after surgery.

Colpotomizer instruments are commonly used in laparoscopic hysterectomy to easily manipulate the uterus. This is the case of a forgotten colpotomy cup retained in the vagina for five years, which led to a rectovaginal fistula. A 54-year-old woman without knowledge of presence of the foreign body visited with chronic abdominal pain and foul odorous discharge. Rectovaginal fistula caused by the retained forgotten colpotomy cup was found upon examination.

Anti-adhesive film mimicking local recurrence during follow up after surgical treatment of gynecologic malignancy.

A 51-year-old woman received a laparoscopic surgical staging operation due to endometrial carcinoma. Adjuvant pelvic radiotherapy was performed when the endometrial carcinoma was staged at FIGO Stage IIIC1, adnexa metastasis. Three months completing adjuvant pelvic radiotherapy, a 2.5-cm vaginal stump mass was found by abdomino-pelvic computed tomography (AP-CT). To rule out local recurrence, diagnostic laparoscopic exploration was performed. The pathologic report revealed chronic inflammation due to the presence of a foreign body. To avoid unnecessary surgery during the follow-up of patients with gynecologic malignancies, anti-adhesive material should be avoided which can possibly cause a lesion mimicking local recurrence.

Pure non-gestational choriocarcinoma arising in the ovary.

Non-gestational choriocarcinoma (NGCO) is a rare primary ovarian cancer with poor prognosis. It is important to distinguish it from gestational ovarian choriocarcinoma (GCO), because there are different treatment options. However, it is difficult to distinguish the two types by routine histologic, ultrastructural, or immunohistochemical examination. The authors present NGCO in a 41-year-old woman, which was confirmed by DNA polymorphism analysis. All tested microsatellite markers had identical DNA profiles with the same allelic sizes between tumor and normal myometrium of the patient, indicating that both tissues originated from the same person. The results confirmed that the tumor was non-gestational in origin. Although the tumor was large, the authors performed hand- assisted laparoscopic surgical (HALS) staging. After three cycles of combination chemotherapy and surgery, the patient has not had any evidence of disease 48 months after treatment. This case demonstrates the usefulness of HALS staging and DNA polymorphism analysis in NGCO.

Factors predicting outcomes of penile rehabilitation with udenafil 50 mg following radical prostatectomy.

Udenafil is a selective phosphodiesterase type 5 inhibitor made available in recent years for the treatment of erectile dysfunction. Herein, we evaluated independent predictors of potency recovery in radical prostatectomy (RP) patients who underwent penile rehabilitation with udenafil 50 mg. One hundred and forty-three men who underwent RP were enrolled in a penile rehabilitation program using udenafil 50 mg every other day. The rate of regained potency in the study group was significantly higher compared with the recovery rate seen in patients who were not part of the penile rehabilitation program (41.3% vs 13.0%; P<0.001). On the multivariate Cox analyses, preoperative International Index of Erectile Function-5 scores (hazard ratio (HR), 1.049; P=0.040), alcohol consumption (HR, 2.043; P=0.020) and Gleason biopsy score (HR, 0.368; P=0.024) were independent preoperative predictors for potency recovery. Among post-RP variables, the use of robotic procedures (HR, 2.287; P=0.030) and pathologic stage (HR, 0.506; P=0.038) were significantly associated with potency recovery. This study identified predictive factors for the recovery of potency in patients undergoing penile rehabilitation with udenafil following RP. Our results could provide physicians with useful information for counseling RP patients and selecting optimal candidates for penile rehabilitation.

ASXL2 promotes proliferation of breast cancer cells by linking ERα to histone methylation.

Estrogen receptor alpha (ERα) has a pivotal role in breast carcinogenesis by associating with various cellular factors. Selective expression of additional sex comb-like 2 (ASXL2) in ERα-positive breast cancer cells prompted us to investigate its role in chromatin modification required for ERα activation and breast carcinogenesis. Here, we observed that ASXL2 interacts with ligand E2-bound ERα and mediates ERα activation. Chromatin immunoprecipitation-sequencing analysis supports a positive role of ASXL2 at ERα target gene promoters. ASXL2 forms a complex with histone methylation modifiers including LSD1, UTX and MLL2, which all are recruited to the E2-responsive genes via ASXL2 and regulate methylations at histone H3 lysine 4, 9 and 27. The preferential binding of the PHD finger of ASXL2 to the dimethylated H3 lysine 4 may account for its requirement for ERα activation. On ASXL2 depletion, the proliferative potential of MCF7 cells and tumor size of xenograft mice decreased. Together with our finding on the higher ASXL2 expression in ERα-positive patients, we propose that ASXL2 could be a novel prognostic marker in breast cancer.

Effects of the jaw-thrust manoeuvre in the semi-sitting position on securing a clear airway during fibreoptic intubation.

Securing a clear airway is important for successful fibreoptic intubation. We investigated whether the jaw-thrust manoeuvre in the 25° semi-sitting position improves airway clearance compared with the supine position in 88 anaesthetised patients randomly assigned to the two positions. After induction of anaesthesia, the fibreoptic bronchoscope was advanced into the mouth along the dorsum of the tongue during the jaw-thrust manoeuvre. Airway clearance was assessed at the level of the soft palate and epiglottis. Patients in the 25° semi-sitting position had clearer airways (judged subjectively by a three-level scale) than those in the supine position at the soft palate level (p = 0.012). At the level of the epiglottis, airway clearance was equally good in both positions. The mean (SD) times to view the vocal cord and carina were shorter in the 25° semi-sitting position (4 (1) s and 8 (1) s, respectively) compared with the supine position (6 (3) s and 11 (3) s; p < 0.001, respectively). The time to achieve intubation was also shorter in the 25° semi-sitting position (21 (5) s) than in the supine position (25 (7) s; p = 0.018).

Electron-boson spectral density of LiFeAs obtained from optical data.

We analyze existing optical data in the superconducting state of LiFeAs at T = 4 K, to recover its electron-boson spectral density. A maximum entropy technique is employed to extract the spectral density I(2)χ(ω) from the optical scattering rate. Care is taken to properly account for elastic impurity scattering which can importantly affect the optics in an s-wave superconductor, but does not eliminate the boson structure. We find a robust peak in I(2)χ(ω) centered about Ω(R) ≅ 8.0 meV or 5.3 k(B)Tc (with Tc = 17.6 K). Its position in energy agrees well with a similar structure seen in scanning tunneling spectroscopy (STS). There is also a peak in the inelastic neutron scattering (INS) data at this same energy. This peak is found to persist in the normal state at T = 23 K. There is evidence that the superconducting gap is anisotropic as was also found in low temperature angular resolved photoemission (ARPES) data.