Tuberculosis in older adults: case studies from four countries with rapidly ageing populations in the western pacific region.

BACKGROUND: The Western Pacific Region has one of the fastest-growing populations of older adults (≥ 65 years) globally, among whom tuberculosis (TB) poses a particular concern. This study reports country case studies from China, Japan, the Republic of Korea, and Singapore reflecting on their experiences in managing TB among older adults. FINDINGS: Across all four countries, TB case notification and incidence rates were highest among older adults, but clinical and public health guidance focused on this population was limited. Individual country reports illustrated a range of practices and challenges. Passive case finding remains the norm, with limited active case finding (ACF) programs implemented in China, Japan, and the Republic of Korea. Different approaches have been trialled to assist older adults in securing an early diagnosis, as well as adhering to their TB treatment. All countries emphasised the need for person-centred approaches that include the creative application of new technology and tailored incentive programs, as well as reconceptualisation of how we provide treatment support. The use of traditional medicines was found to be culturally entrenched among older adults, with a need for careful consideration of their complementary use. TB infection testing and the provision of TB preventive treatment (TPT) were underutilised with highly variable practice. CONCLUSION: Older adults require specific consideration in TB response policies, given the burgeoning aging population and their high TB risk. Policymakers, TB programs and funders must invest in and develop locally contextualised practice guidelines to inform evidence-based TB prevention and care practices for older adults.

Ultrasonography is an effective tool for the evaluation of traumatic vertebral artery injuries distal to fourth cervical vertebra in the emergency room.

BACKGROUND: This study aimed to determine the feasibility of ultrasonography in the assessment of cervical vertebral artery (VA) injury as an alternative to computed tomography angiography (CTA) in the emergency room. METHODS: We analyzed 50 VAs from 25 consecutive patients with cervical spine injury that had been admitted to our emergency room. Ultrasonography and CTA were performed to assess the VA in patients with cervical spine injury. We examined the sensitivity and specificity of ultrasonography compared with CTA. RESULTS: Among these VAs, six were occluded on CTA. The agreement between ultrasonography and CTA was 98% (49/50) with 0.92 Cohen's Kappa index. The sensitivity, specificity, and positive and negative predictive values of ultrasonography were 100%, 97.7%, 85.7%, and 100%, respectively. In one case with hypoplastic VA, the detection of flow in the VA by ultrasonography differed from detection by CTA. Meanwhile, there were two cases in which VAs entered at C5 transverse foramen rather than at C6 level. However, ultrasonography could detect the blood flow in these VAs. CONCLUSIONS: Ultrasonography had a sensitivity of 100% compared with CTA in assessment of the VA. Ultrasonography can be used as an initial screening test for VA injury in the emergency room.

[A 30-Month Survival Case of Undifferentiated Carcinoma of the Duodenum Treated by Pancreaticoduodenectomy].

The patient was an elderly man in his early 80s who was admitted to our hospital due to anemia and tarry stools. An upper gastrointestinal endoscopy revealed a type 2 tumor in the second portion of the duodenum. An endoscopic biopsy revealed poorly differentiated adenocarcinoma. We performed a pancreaticoduodenectomy because neither lymphadenopathy nor distant metastases were found. Macroscopic findings revealed that the lesion was mainly in the second portion of the duodenum, and there was no evidence of invasion of the main pancreatic duct, the bile duct, or the ampulla of Vater. Histologically, the tumor was composed of atypical cells with polymorphic or spindle-shaped nuclei proliferating in a scattered fashion, and immunohistological examinations showed weakly positive results for cytokeratin(CK)AE1/AE3 and CK20 and positive results for vimentin but negative results for CK7. The tumor was diagnosed as undifferentiated carcinoma of the duodenum(pT4N0M0, pStage ⅡB). The patient recovered enough to be discharged and was followed up without postoperative adjuvant chemotherapy. He maintained recurrence-free survival for 27 months, after which lymph node and lung metastases reoccurred. This is a rare case of undifferentiated carcinoma of the duodenum treated by curative resection with a relatively favorable prognosis.

Pentraxin 3 is an adipose tissue-related serum marker for pancreatic cancer cachexia predicting subsequent muscle mass and visceral fat loss.

Cancer cachexia, a paraneoplastic syndrome characterized by ongoing skeletal muscle mass loss, is accompanied by adipose tissue loss and strongly affects chemotherapy endurance. Our aim was to detect a serum marker reflecting pancreatic cancer cachexia and predicting subsequent loss of muscle mass and adipose tissue, focusing on adipose tissue-secreted proteins. Murine-derived pancreatic cancer cells were orthotopically injected into the mouse pancreatic tail. After 3 weeks, RNA sequencing of perigonadal fat and orthotopic tumors was carried out. We analyzed stocked sera and clinical data of metastatic pancreatic cancer patients who received chemotherapy. Perigonadal fat weight/body weight decreased in mice with orthotopic tumors compared to those without tumors. By RNA sequencing and real-time PCR validation, pentraxin 3 (PTX3) was identified as a secreted protein-encoded gene whose expression was significantly higher in the perigonadal fat of mice with orthotopic tumors than in that of mice without orthotopic tumors and was least expressed in orthotopic tumors. Serum PTX3 levels correlated with PTX3 mRNA levels in perigonadal fat and were higher in mice with orthotopic tumors than in those without tumors. In 84 patients diagnosed with metastatic pancreatic cancer, patients with high serum PTX3 levels showed a greater visceral fat loss/month and skeletal muscle mass index (SMI) decrease/month than those with low serum PTX3 levels. High serum PTX3 was an independent risk factor for visceral fat loss, decreased SMI, and poor prognosis. High serum PTX3 in pancreatic cancer patients predicts visceral fat and muscle mass loss and major clinical outcomes of cancer cachexia.

Pancreatic hamartoma: detection of harbouring NAB2::STAT6 fusion gene.

Hamartomas in the pancreas are rare and are often histologically and morphologically similar to solitary fibrous tumours (SFTs). We examined the differences between hamartomas and SFTs at the molecular level. METHODS AND RESULTS: Thirteen patients histopathologically diagnosed with pancreatic hamartoma were included in the study. We also performed STAT6 immunohistochemistry (IHC), which is used in the diagnosis of SFT. Furthermore, for the three cases in which RNA was extracted, reverse transcription polymerase chain reaction to search for NAB2::STAT6 fusions was used. Macroscopically, 13 patients had well-demarcated tumour lesions. Histologically, no islets of Langerhans were observed in the lesions, acinar tissue and ducts were unevenly distributed and elastic fibres were not observed around the ducts by Elastica van Gieson staining. One case contained a lipomatous hamartoma composed mainly of adipose tissue. Seven of the 13 cases demonstrated expression of STAT6 in the nuclei of intervening spindle cells. NAB2::STAT6 fusions were observed in two of the three cases in which RNA was extracted. These two cases also demonstrated STAT6 expression in spindle cells using STAT6 IHC. In one case of lipomatous hamartoma, we did not confirm NAB2::STAT6 fusion or STAT6 expression in STAT6 IHC. CONCLUSION: Of the 13 patients histopathologically diagnosed with hamartoma, two demonstrated NAB2::STAT6 fusions, suggesting the existence of pancreatic hamartomas with molecular-level components identical to those of SFT.

Diagnostic accuracy of the interferon-gamma release assay in acquired immunodeficiency syndrome patients with suspected tuberculosis infection: a meta-analysis.

PURPOSE: The diagnostic accuracy of the interferon-gamma release assay (IGRA) in immunosuppressed patients remains unclear. METHODS: A systematic review and meta-analysis were performed for diagnostic test accuracy of IGRA in tuberculosis (TB) infection among people living with HIV (PLWHIV). Summary estimates of sensitivity and specificity were calculated using both univariate and bivariate models. RESULTS: The meta-analysis included 45 of the 1,242 first-screened articles. The total number of PLWHIV was 6,525; 3,467 had TB disease, including 806 cases of LTBI and 2,661 cases of active TB. The overall diagnostic odds ratio (DOR) of IGRA in the diagnosis of TB disease was 10.0 (95% confidence interval (CI) 5.59, 25.07), with an area under the curve (AUC) of 0.729. The DOR was better for QFT (14.2 (95%CI 4.359, 46.463)) than T-SPOT (10.0 (95%CI 3.866 26.033)). The sensitivity and specificity of QFT and T-SPOT were 0.663 (95%CI 0.471, 0.813), 0.867 (95%CI 0.683 0.942), and 0.604 (95%CI 0.481, 0.715), 0.862 (95%CI 0.654, 0.954), respectively, in the bivariate model. The sensitivity of IGRA in the diagnosis of LTBI was 0.64 (95%CI 0.61, 0.66). CONCLUSION: IGRA was useful in the diagnostic of TB disease in PLWHIV, and QFT showed a better tendency of DOR than T-SPOT. IGRA showed a limited effect to rule out LTBI in PLWHIV.

Synthesis and Configuration Confirmation of the ATHOD Fatty Amino Acid Residue in the Burkholdines.

Eight possible diastereomers of the 3-amino-5,6,7-trihydroxy octadecanoic acid (ATHOD) moiety of the burkholdines (Bks) have been synthesized and their configurations assigned. Though the relative configuration of the triol in the ATHOD residue of the Bks was proposed to be anti-anti-anti in the literature, 1H NMR spectra of our synthesized anti-anti-anti ATHOD derivative was inconsistent with that of the isolated ATHOD residue, suggesting that the assignment of the relative configuration of that residue in the literature was incorrect. However, by comparison of the NMR data of our ATHOD derivatives with that of configurationally defined samples of 2-amino-4-pentanol using Kishi's NMR database method, we conclude that the absolute configuration of the ATHOD moiety is (3R,5S,6R,7S). In addition, we revealed that the ATHOD residue present in the occidiofungins A-D has the same configuration as that in all the Bks.

Multisystem inflammatory syndrome in adults after acute coronavirus disease 2019 in a Japanese woman: A case report.

Multisystem inflammatory syndrome in adults (MIS-A) is a rare and emerging syndrome after coronavirus disease 2019 (COVID-19). To the best of our knowledge, Japanese cases of MIS-A are rarely reported. Here, we describe a case of MIS-A in a 44-year-old Japanese woman presenting with multiorgan dysfunction (i.e., cardiovascular and mucocutaneous involvement) and markedly elevated inflammatory markers 2 weeks after recovery from COVID-19. Treatment with intravenous immunoglobulins and corticosteroids resolved her symptoms. On the 13th day, she was discharged from the hospital with no recurrences on follow-up. This study highlights the importance of recognizing this emerging syndrome when treating patients with multiorgan dysfunction after COVID-19.

Renal Leukemic Infiltration Overlapping Acute Focal Bacterial Nephritis during Myelodysplastic Syndrome: An Autopsy Case Report.

Renal leukemic infiltration is uncommon in myeloid neoplasms, including myelodysplastic syndromes (MDS). A 76-year-old male patient was admitted to our hospital with complaints of fever and dyspnea. He was diagnosed with MDS with multilineage dysplasia and acute focal bacterial nephritis (AFBN) based on clinical, laboratory, and radiological investigations. Antibiotic treatment temporarily improved his condition, but the radiological image of AFBN remained. His condition gradually deteriorated into multiple organ failure, and he unfortunately died on the 31st day of hospitalization. Autopsy findings revealed significantly increased p53-positive blasts in the bone marrow and renal parenchyma overlapping AFBN, suggesting leukemic transformation and renal infiltration. This case emphasizes the need to review the diagnosis when antibiotic treatment is ineffective in MDS patients with AFBN.

Multidrug Resistant Tuberculosis With Simultaneously Acquired Drug Resistance to Bedaquiline and Delamanid.

This study is the first to report a clinical case of simultaneously acquired resistance to bedaquiline (BDQ) and delamanid (DLM). Whole genome sequencing revealed 2 nucleotide insertions (Rv0678 and fbiC) in the Mycobacterium tuberculosis isolate. The minimum inhibitory concentrations for BDQ and DLM were 0.25 µg/mL and >2.0 µg/mL, respectively.

Prevalence of SARS-CoV-2-Specific Antibodies, Japan, June 2020.

We used 2 commercially available antibody tests to estimate seroprevalence of severe acute respiratory syndrome coronavirus 2 infection in Japan during June 2020. Of 7,950 samples, 8 were positive by both assays. Using 2 reliable antibody tests in conjunction is an effective method for estimating seroprevalence in low prevalence settings.

Prehospital Blood Pressure and Lactate are Early Predictors of Acute Kidney Injury After Trauma.

BACKGROUND: The purpose of this study is to report the prevalence of acute kidney injury (AKI) after trauma in our center, describe the risk factors associated with AKI, and determine whether these risk factors help avoid AKI. MATERIALS AND METHODS: We retrospectively analyzed the data which were prospectively collected from a single center trauma registry from January 2017 to December 2018. Patients who were <16 years of age, patients with burns, and patients with chronic kidney disease were excluded from the present study. AKI was defined according to the risk, injury, failure, loss of the kidney function, and end-stage kidney disease (RIFLE) classification from serum creatinine alone. A logistic regression analysis was performed to identify prehospital and early hospital risk factors for AKI. RESULTS: There were 806 trauma patients recorded in the database. One hundred thirty cases were excluded based on the abovementioned exclusion criteria. Six hundred seventy-six patients were included in the analysis. The prevalence of AKI in the overall population was 14.5% including 10.5% of patients with stage R, 3.0% of patients with stage I and 1.0% with stage F. The incidence of AKI increased to 36.3%, 12.1% and 3.3% in the subgroup of patients with hemorrhagic shock. The multivariate analysis revealed that the minimum prehospital systolic blood pressure and arterial lactate level were independent predictors of AKI. The model showed good discrimination with an area under the receiver operating characteristic curve (AUC-ROC) of 0.867 and 0.852 in the prediction of AKI stage I or F. The cutoff values were ≤126 mmHg and ≥2.5 mmol/L, respectively. CONCLUSION: These parameters showed good performance in the early prediction of AKI after trauma. They are associated with the early onset of AKI after trauma and may be an early predictor of the effects of treatment to prevent AKI.

Femtosecond PLD-grown YF3 nanoparticle thin films as improved filterless VUV photoconductive detectors.

A photoconductive detector (PCD) responding only to vacuum ultraviolet (VUV) radiations below 180 nm without any filter was fabricated using an yttrium fluoride (YF3) thin film grown by femtosecond (fs) laser pulsed laser deposition (PLD). The structural morphology (particle size and surface roughness) of the thin film was improved using a low laser fluence and a high substrate temperature during the fabrication. The smallest average particle size achieved was 159 nm with a roughness of 37 nm at a laser fluence of 13.5 J cm-2 and a substrate temperature of 400 °C. The resistances for the dark current of the PCD increased from 10 TΩ to 680 TΩ using YF3 thin films with a smaller average nanoparticle diameter of 159 nm rather than 330 nm. The time response of the PCD to a VUV flash lamp emitting at 170 nm showed that a small average nanoparticle diameter results to a fast response time. By covering the Al electrode pairs with another fs PLD-grown YF3 film, the influence of external photoelectric effect was suppressed and the response wavelength edge decreased from 280 nm to 180 nm without any filter. The filterless PCD is expected to enhance the use of fluoride thin films in conjunction with VUV light sources for various scientific and industrial applications.

Parafunctional masseter muscle activity during waking is related to periodontitis progression: A pilot prospective cohort study.

AIM: The purpose of this pilot prospective cohort study was to investigate the effects of parafunctional masseter muscle activity on periodontitis progression among patients receiving supporting periodontal therapy (SPT). MATERIALS AND METHODS: We collected data of patients treated at Okayama University Hospital from August 2014 to September 2018. The progression group was defined as patients with ≥2 teeth demonstrating a longitudinal loss of proximal attachment of ≥3 mm during the 3-year study period and/or at least one tooth extraction due to periodontitis progression. Surface electromyography of masseter muscles at baseline was continuously recorded while patients were awake and asleep. RESULTS: We analysed 48 patients (36 females) aged 66.8 ± 9.1 years (mean ± SD). The rate of parafunctional masseter muscle activity during waking hours and sleeping hours at baseline was 60.4% and 52.1%, respectively. Cox's proportional hazards regression model showed that the incidence of periodontitis progression was significantly associated with number of teeth present (p = 0.001) and parafunctional masseter muscle activity during waking hours (p = 0.041). CONCLUSION: Our results suggest that parafunctional masseter muscle activity during waking hours is a risk factor for periodontitis progression among patients receiving SPT.

Coronavirus disease (COVID-19) associated delayed-onset fulminant myocarditis in patient with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

A healthy 35-year-old man was admitted to a rural hospital with coronavirus disease (COVID-19). During 14 days of hospitalization, he had no symptoms and was not given supplemental oxygen. About 3 weeks after discharge, he was re-admitted to the same hospital with new-onset continuous fever and general weakness. At the time of his second admission, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RT-PCR was performed on a retro-nasal swab and the result was negative. Four days after admission, the patient was transferred to our intensive care unit (ICU) following deterioration of his respiratory and haemodynamic conditions, where he received mechanical ventilation, intra-aortic balloon pumping, and veno-arterial extracorporeal membrane oxygenation. A nasopharyngeal swab was obtained again at ICU admission, but RT-PCR was negative for SARS-CoV-2. All antibody titres measured against other viruses were low. Blood cultures were negative, and no bacteria were observed in sputum samples. However, SARS-CoV-2 RNA was detected by RT-PCR from sections obtained by myocardial biopsy. The patient's final diagnosis was delayed-onset SARS-CoV-2-induced fulminant myocarditis (FM). We strongly suggested that one of the proposed mechanisms of COVID-19-related myocardial injury will be the direct invasion of SARS-CoV-2 into cardiomyocytes even if delayed-onset. And this is the first case of delayed-onset FM in which diagnosis of active myocarditis was proven by pathological examination following endomyocardial biopsy and SARS-CoV-2 was detected in the myocardium by RT-PCR.

Is open abdominal management useful in nontrauma emergency surgery for older adults? A single-center retrospective study.

PURPOSE: Open abdominal management (OAM) is being adopted increasingly frequently in nontrauma patients. This study assessed the effectiveness of OAM in nontrauma older adults. METHODS: We retrospectively reviewed all adults who underwent nontrauma emergency laparotomy requiring postoperative intensive care unit (ICU) management between September 2012 and August 2017 at our hospital. Patients ≥ 80 years old, who underwent OAM, were compared with those < 80 years old. The primary outcome was the 90-day mortality. Secondary outcomes were the 30-day mortality, unplanned relaparotomy, and the ICU length of stay (LOS). RESULTS: The OAM group comprised 58 patients, including 27 who were ≥ 80 years old. The patients ≥ 80 years old in the OAM group had a significantly higher 90-day mortality rate (33% vs. 10%; p = 0.027) than those < 80 years old. There were no significant differences in the 30-day mortality rate, patients' unplanned relaparotomy rate, or ICU LOS between the patients ≥ 80 years old and those < 80 in the OAM group. CONCLUSIONS: Older adults who underwent OAM had a significantly higher mortality rate than younger patients. However, the OAM strategy for older nontrauma patients may still be useful and reasonable considering the severe condition of these patients.

Timely intubation with early prediction of respiratory exacerbation in acute traumatic cervical spinal cord injury.

BACKGROUND: Early routine intubation in motor-complete cervical spinal cord injury (CSCI) above the C5 level is a conventional protocol to prevent unexpected respiratory exacerbation (RE). However, in the context of recent advances in multidisciplinary respiratory management, the absolute indication for intubation in patients with CSCI based on initial neurologic assessment is controversial because of the drawbacks of intubation. This study aimed to redetermine the most important predictor of RE following CSCI after admission without routine intubation among patients admitted with motor-complete injury and/or injury above the C5 level to ensure timely intubation. METHODS: We performed a retrospective review of patients with acute traumatic CSCI admitted to our hospital without an initial routine intubation protocol from January 2013 to December 2017. CSCI patients who developed RE (defined as unexpected emergent intubation for respiratory resuscitation) were compared with those who did not. Baseline characteristics and severity of trauma data were collected. Univariate analyses were performed to compare treatment data and clinical outcomes between the two groups. Further, multivariate logistic regression was performed with clinically important independent variables: motor-complete injury, neurologic level above C5, atelectasis, and copious airway secretion (CAS). RESULTS: Among 58 patients with CSCI, 35 (60.3%) required post-injury intubation and 1 (1.7%) died during hospitalization. Thirteen (22.4%) had RE 3.5 days (mean) post-injury; 3 (37.5%) of eight patients with motor-complete CSCI above C5 developed RE. Eleven of the 27 (40.7%) patients with motor-complete injury and five of the 22 (22.7%) patients with neurologic injury above C5 required emergency intubation at RE. Three of the eight CSCI patients with both risk factors (motor-complete injury above C5) resulted in emergent RE intubation (37.5%). CAS was an independent predictor for RE (odds ratio 7.19, 95% confidence interval 1.48-42.72, P = 0.0144) in multivariate analyses. CONCLUSION: Timely intubation post-CSCI based on close attention to CAS during the acute 3-day phase may prevent RE and reduce unnecessary invasive airway control even without immediate routine intubation in motor-complete injury above C5.

The Association Between Sequential Organ Failure Assessment Scores and Mortality in Patients With Sepsis During the First Week: The JSEPTIC DIC Study.

OBJECTIVE: Predicting prognosis is a complex process, particularly in patients with severe sepsis or septic shock. This study aimed to determine the relationship between the Sequential Organ Failure Assessment (SOFA) scores for individual organs during the first week of admission and the in-hospital mortality in patients with sepsis. METHODS: This study was a post hoc evaluation of the Japan Septic Disseminated Intravascular Coagulation study and included patients admitted to 42 intensive care units in Japan for severe sepsis or septic shock, between January 2011 and December 2013. We assessed the relationship between the organ and total SOFA scores on days 1, 3, and 7 following admission and the in-hospital mortality using logistic regression analysis. RESULTS: We evaluated 2732 patients and found the in-hospital mortality rate was 29.1%. The mean age of the patients (standard deviation) was 70.5 (14.1) years, and the major primary site of infection was the abdomen (33.6%). The central nervous system (CNS) SOFA score exhibited the strongest relationship with mortality on days 1 (adjusted odds ratio [aOR]: 1.49, 95% confidence interval [CI]: 1.40-1.59), 3 (aOR: 1.75, 95% CI: 1.62-1.89), and 7 (aOR: 1.93, 95% CI: 1.77-2.10). The coagulation SOFA scores showed a weak correlation with mortality on day 1, but a strong correlation with mortality on day 7 (aOR: 2.04, 95% CI: 1.87-2.24). CONCLUSIONS: The CNS SOFA scores were associated with mortality in patients with severe sepsis on days 1, 3, and 7 following hospitalization. The coagulation SOFA score was associated with mortality on day 7. In clinical situations, the CNS SOFA scores during the acute phase and the CNS SOFA and coagulation SOFA scores during the subsequent phases should be evaluated in order to determine patient prognosis.

The effect of positive-end-expiratory pressure on stroke volume variation: An experimental study in dogs.

Stroke volume variation (SVV) may be affected by ventilation settings. However, it is unclear whether positive-end-expiratory pressure (PEEP) affects SVV independently of the effect of driving pressure. We aimed to investigate the effect of driving pressure and PEEP on SVV under various preload conditions using beagle dogs as the animal model. We prepared three preload model, baseline, mild and moderate haemorrhage model. Mild and moderate haemorrhage models were created in nine anaesthetized, mechanically ventilated dogs by sequentially removing 10 mL/kg, and then an additional 10 mL/kg of blood, respectively. We measured cardiac output, stroke volume (SV), SVV, heart rate, central venous pressure, pulmonary capillary wedge pressure and the mean arterial pressure under varying ventilation settings. Peak inspiratory pressure (PIP) was incrementally increased by 4 cmH2 O, from 9 cmH2 O to 21 cmH2 O, under PEEP values of 4, 8, and 12 cmH2 O. The driving pressure did not significantly decrease SV under each preload condition and PEEP; however, significantly increased SVV. In contrast, the increased PEEP decreased SV and increased SVV under each preload condition and driving pressure, but these associations were not statistically significant. According to multiple regression analysis, an increase in PEEP and decrease in preload significantly decreased SV (P < .05). In addition, an increase in the driving pressure and decrease in preload significantly increased SVV (P < .05). Driving pressure had more influence than PEEP on SVV.

Synthesis of a burkholdine analogue containing ß-hydroxytyrosine.

Synthesis of a ß-OHTyr-containing Bk analogue, a cyclic octalipopeptide with antifungal activities, is described. Since ß-OHTyr-containing peptides generally are unstable in strong acidic conditions, synthesis of ß-HOTyr-containing peptides by SPPS have rarely been reported. To overcome this problem, we found that using distilled TFA removed the protecting groups of side chains of ß-OHTyr-containing Bk analogue, which was prepared by Fmoc-SPPS. Abbreviations: ß-OHTyr: ß-hydroxytyrosine; ß-OHAsn: ß-hydroxyasparagine; Bk: burkholdine; FAA: fatty acyl amino acid; ß-MeOTyr: ß-methoxytyrosine; SPPS: solid phase peptide synthesis; MIC: minimun inhibitory concentration; DMF: dimethyl formamide; DIPEA: diisopropylethylamine; DIPC: diisopropylcarbodiimide; HOBt: 1-hydroxybenzotriazole; Fmoc: 9-fluorenylmethyloxycarbonyl; HFIP: 1,1,1,3,3,3-hexafluoropropan-2-ol; TFA: trifluoroacetic acid; LAP: N-lauryl -3-amino-4-carbamolypropanoic acid; HPLC: high performance liquid chromatography; ESI-TOFMS: electrospray ionization-time of flight mass spectrometry; Bn: benzyl; Boc: t-butyloxycatbonyl; 2-CTC: 2-chlorotritylchloride.