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Background. The association between economic status and kidney disease is incompletely explored even in countries with higher economy (HE); the situation is complex in lower economies (LE) of South Asia and Southeast Asia (SA and SEA). Methods. Fifteen countries of SA and SEA categorized as HE and LE, represented by the representatives of the national nephrology societies, participated in this questionnaire and interview-based assessment of the impact of economic status on renal care. Results. Average incidence and prevalence of end-stage kidney disease (ESKD) per million population (pmp) are 1.8 times and 3.3 times higher in HE. Hemodialysis is the main renal replacement therapy (RRT) (HE-68%, LE-63%). Funding of dialysis in HE is mainly by state (65%) or insurance bodies (30%); out of pocket expenses (OOPE) are high in LE (41%). Highest cost for hemodialysis is in Brunei and Singapore, and lowest in Myanmar and Nepal. Median number of dialysis machines/1000 ESKD population is 110 in HE and 53 in LE. Average number of machines/dialysis units in HE is 2.7 times higher than LE. The HE countries have 9 times more dialysis centers pmp (median HE-17, LE-02) and 16 times more nephrologist density (median HE-14.8 ppm, LE-0.94 ppm). Dialysis sessions >2/week is frequently followed in HE (84%) and 10% in all the HE countries except Taiwan, 10%–20% in the majority of LE countries. Conclusion. Economic disparity in SA and SEA is reflected by poor dialysis infrastructure and penetration, inadequate manpower, higher OOPE, higher dialysis dropout rates, and lesser renal transplantations in LE countries. Utility of RRT can be improved by state funding and better insurance coverage.

Objective: There is limited safety data on the use of everolimus during pregnancy. In this study, we present the maternal and neonatal outcomes of everolimus used throughout the course of pregnancy and conducted a systematic review of reports of everolimus use after organ transplantation during pregnancy., Case Report: A woman with type 1 diabetes who underwent kidney transplantation was treated with tacrolimus, everolimus, and prednisolone. Two years later, she became pregnant. At 27 weeks of gestation, an emergent cesarean delivery was performed owing to severe preeclampsia and fetal distress. No congenital malformation was noted in the baby at a corrected age of 4 months, and the maternal renal function remained stable., Conclusion: Our systematic review did not identify evidence of teratogenicity in babies exposed to everolimus as an immunosuppressant after transplantation. To better assess the risk of exposure to everolimus during pregnancy, all cases of new pregnancies occurring in transplant recipients receiving treatment with mammalian target of rapamycin inhibitor inhibitors should be reported., Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Potato common scab, which is mainly caused by the bacterium Streptomyces scabies , occurs in key potato growing regions worldwide. It causes necrotic or corky symptoms on potato tubers and decreases the economic value of potato. At present, there is no recommended chemical or biological control for combating potato common scab in Taiwan. It can only reduce the occurrence by cultivation control, but the efficacy is limited. Previously we found that Bacillus amyloliquefaciens Ba01 could control potato common scab in pot assay and in the field. The potential anti- S. scabies mechanism was associated with surfactin secretion, but further molecular dissection was not conducted. Thus, in this study we aimed to determine whether surfactin is the main compound active against S. scabies by knocking out the srf gene cluster in Ba01. The cloning plasmid pRY1 was transformed to Ba01 by electroporation for in-frame deletion. Two independent Δ srf mutants were obtained and confirmed by specific primers and mass spectrometry. The swarming ability and S. scabies inhibition was significantly decreased ( P <0.001) in Δ srf mutants. The swarming ability of Δ srf mutants could be restored by the addition of surfactin. Furthermore, we found that Ba01 formed wrinkled biofilm in MSgg liquid medium, while Δ srf mutants formed biofilm abnormally. Furthermore, the α-amylase, protease and phosphate-solubilizing ability of Δ srf mutants was decreased, and the mutants could not inhibit the growth and sporulation of S. scabies on potato tuber slices. In conclusion, srf gene cluster of B. amyloliquefaciens Ba01 is responsible for the secretion of surfactin and inhibition of S. scabies ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Feng, Chen, Lin, Tsai, Yang and Chen.)

Bacterial polyynes are highly active natural products with a broad spectrum of antimicrobial activities. However, their detailed mechanism of action remains unclear. By integrating comparative genomics, transcriptomics, functional genetics, and metabolomics analysis, we identified a unique polyyne resistance gene, masL (encoding acetyl-CoA acetyltransferase), in the biosynthesis gene cluster of antifungal polyynes (massilin A 1, massilin B 2, collimonin C 3, and collimonin D 4) of Massilia sp. YMA4. Crystallographic analysis indicated that bacterial polyynes serve as covalent inhibitors of acetyl-CoA acetyltransferase. Moreover, we confirmed that the bacterial polyynes disrupted cell membrane integrity and inhibited the cell viability of Candida albicans by targeting ERG10, the homolog of MasL. Thus, this study demonstrated that acetyl-CoA acetyltransferase is a potential target for developing antifungal agents., (© 2022. The Author(s).)

Neonatal candidemia is associated with significant morbidities and a high mortality rate. We aimed to investigate the clinical characteristics of Candida bloodstream infections in neonates and the impact of therapeutic strategies on the outcomes. We identified all the neonates with candidemia from a medical center in Taiwan over an 18-year period (2003−2021) and analyzed them. Clinical isolates were confirmed by DNA sequencing, and antifungal susceptibility testing was performed. The prognostic factors associated with clinical treatment failure (30-day, all-cause mortality and persistent candidemia > 72 h after antifungal agents) and in-hospital mortality were analyzed using logistic regression modeling. A total of 123 neonates with 139 episodes of candidemia were included in the study. The median (IQR) gestational age and birth weight of the neonates with candidemia were 29.0 (26.0−35.0) weeks and 1104.0 (762.0−2055) g, respectively. The most common Candida spp. was Candida albicans (n = 57, 41.0%), followed by C. parapsilosis (n = 44, 31.7%), Candida guilliermondii (n = 12, 8.6%), and C. glabrata (n = 11, 7.9%). The overall susceptibility to fluconazole was 81.3%, and the resistant rates against other antifungal agents were less than 3%. The cumulative mortality rate at 7 and 30 days after the first episode of candidemia was 11.3% and 32.3%, respectively. The overall in-hospital mortality rate was 42.3%. The treatment outcomes did not change over the study period and were not affected by delayed initiation of antifungal agents. Multivariate analysis showed that delayed catheter removal (odds ratio [OR], 5.54; 95% confidence interval [CI]: 1.93−15.86, p = 0.001), septic shock (OR, 7.88; 95% CI: 2.83−21.93, p < 0.001), and multiple chronic comorbidities (OR, 8.71; 95% CI: 1.82−41.81, p = 0.007) were independently associated with the final in-hospital mortality. We concluded that the overall mortality of neonatal candidemia has remained consistently high over the past decade. Prompt early catheter removal and an aggressive treatment strategy for neonatal candidemia with septic shock would be critical to improving patient outcomes.

Colletotrichum gloeosporioides is a phytopathogenic fungus that causes devastating losses in strawberries without effective countermeasures. Members of the genus Photorhabdus exhibit antimicrobial capability and have been found to have the potential for use as biocontrol agents against C. gloeosporioides . Photorhabdus species exhibit two phase variations with a differentiated composition of secondary metabolites designated to each phase. In this study, Photorhabdus akhurstii sp. nov. 0813-124 exhibited phase I (PL1) and phase II (PL2); however, only PL1 displayed distinct inhibition of C. gloeosporioides in the confrontation assay. We identified the bioactive ingredients of P. akhurstii sp. nov. 0813-124 to be glidobactin A and cepafungin I, with MIC values lower than 1.5 and 2.0 µg/mL, respectively. Furthermore, we revealed the biosynthetic gene cluster (BGC) of corresponding bioactive molecules through genomics analysis and determined its expression level in PL1 and PL2. The expression of glidobactin BGC in PL1 increased rapidly within 24 h, while PL2 was eventually stimulated after 60 h. In summary, we demonstrated that P. akhurstii sp. nov. 0813-124 could potentially be used as a biocontrol agent or part of a natural product repertoire for combating C. gloeosporioides .

Introduction: Neurodevelopmental impairment is a growing concern for preterm infants who received surgical ligation of patent ductus arteriosus (PDA). We aimed to explore the cerebral hemodynamics during the critical period of PDA ligation., Methods: Very-low-birth-weight (VLBW) preterm infants who underwent PDA ligation were prospectively enrolled. Patients were monitored preoperatively and until 72 h post-ligation. Middle cerebral artery (MCA) flow, regional cerebral oxygen saturation (rcSO2), and cardiac output were measured through Doppler ultrasound, near-infrared spectroscopy, and electrical cardiometry, respectively. Using rcSO2 <55% indicating cerebral hypoxia, the duration (% of time) and burden (cumulative negative quantity of rsSO2 <55% × the period [minutes]) were estimated. An abnormal MCA was defined as an MCA flow of <10th percentile of flow velocity or >90th percentile of pulsatility or resistance index. Poor outcomes were defined as in-hospital death or neurologic disorders, either neuroimaging or functional abnormalities, upon discharge., Results: Thirty-two VLBW infants were examined, and 15 (46.9%) had poor outcomes. Infants with poor outcomes had significantly longer duration of cerebral hypoxia (5.4 [2.2-32.3] vs. 1.8 [0.4-5.6] %, p = 0.033) and worse hypoxic burden (2,118 [684-13,549] vs. 622 [88-1,669] %minutes, p = 0.027). In a linear mixed model, rcSO2 was positively correlated with arterial saturation (β 0.860, 95% CI: 0.649-1.070) and negatively correlated with abnormal MCA flow (β -5.287, 95% CI: -8.238 to -2.335)., Conclusion: Longer duration of cerebral hypoxia and worse hypoxic burden post-ligation was associated with an increased risk of in-hospital mortality or neurologic disorders upon discharge in VLBW preterm infants., (© 2022 S. Karger AG, Basel.)

Group B Streptococcus (GBS) is an important pathogen of neonatal infections, and the clonal complex (CC)-17/serotype III GBS strain has emerged as the dominant strain. The clinical manifestations of CC17/III GBS sepsis may vary greatly but have not been well-investigated. A total of 103 CC17/III GBS isolates that caused neonatal invasive diseases were studied using a new approach based on clustered regularly interspaced short palindromic repeats (CRISPR) loci and restriction fragment length polymorphism (RFLP) analyses. All spacers of CRISPR loci were sequenced and analyzed with the clinical presentations. After CRISPR-RFLP analyses, a total of 11 different patterns were observed among the 103 CRISPR-positive GBS isolates. GBS isolates with the same RFLP patterns were found to have highly comparable spacer contents. Comparative sequence analysis of the CRISPR1 spacer content revealed that it is highly diverse and consistent with the dynamics of this system. A total of 29 of 43 (67.4%) spacers displayed homology to reported phage and plasmid DNA sequences. In addition, all CC17/III GBS isolates could be categorized into three subgroups based on the CRISPR-RFLP patterns and eBURST analysis. The CC17/III GBS isolates with a specific CRISPR-RFLP pattern were more significantly associated with occurrences of severe sepsis (57.1% vs. 29.3%, p = 0.012) and meningitis (50.0% vs. 20.8%, p = 0.009) than GBS isolates with RFLP lengths between 1000 and 1300 bp. Whole-genome sequencing was also performed to verify the differences between CC17/III GBS isolates with different CRISPR-RFLP patterns. We concluded that the CRISPR-RFLP analysis is potentially applicable to categorizing CC17/III GBS isolates, and a specific CRISPR-RFLP pattern could be used as a new biomarker to predict meningitis and illness severity after further verification.

Background: Streptococcus agalactiae (also known as group B streptococcus, GBS) is associated with high mortality and morbidity rates in infants, especially those with complicated GBS sepsis, defined as those with meningitis, severe sepsis and/or septic shock. We aimed to characterize the clinical and molecular characteristics and risk factors for adverse outcomes of neonates with invasive GBS diseases., Methods: From 2003 to 2020, all neonates with invasive GBS diseases who were hospitalized in a tertiary-level neonatal intensive care unit (NICU) were enrolled. The GBS isolates underwent serotyping, multilocus sequence typing (MLST) and antibiotic susceptibility testing. We compared cases of complicated GBS sepsis with uncomplicated GBS bacteremia., Results: During the study period, a total of 188 neonates (aged less than 6 months old) with invasive GBS diseases were identified and enrolled. Among them, 119 (63.3%) had uncomplicated GBS bacteremia and 69 (36.7%) neonates had complicated GBS sepsis, including meningitis (25.5%, n = 48) and severe sepsis or septic shock. Among neonates with complicated GBS sepsis, 45 (65.2%) had neurological complications, and 21 (42.0%) of 50 survivors had neurological sequelae at discharge. The overall final mortality rate was 10.1% (19 neonates died). Type III/ST-17 GBS isolates accounted for 56.5% of all complicated GBS sepsis and 68.8% of all GBS meningitis, but this strain was not significantly associated with worse outcomes. The antimicrobial resistance rate among the invasive GBS isolates was obviously increasing in the past two decades. After multivariate logistic regression analysis, neonates with thrombocytopenia and respiratory failure were independently associated with final adverse outcomes., Conclusions: a total of 36.7% of all neonatal invasive GBS diseases were associated with complicated sepsis with/without meningitis. Given the high mortality and morbidity rates in neonates with complicated GBS sepsis, further studies for early identification of specific strains, risk factors or genetic mechanisms that will cause complicated GBS sepsis are urgently needed in the future.

The Coronavirus Disease-2019 (COVID-19) pandemic has brought catastrophic impact on the world since the beginning of December 2019. Extra precautionary measures against COVID-19 during and after delivery are pivotal to ensure the safety of the baby and health care workers. Based on current literature, it is recommended that delivery decisions be discussed between obstetricians and neonatologists prior to delivery, and designated negative pressure delivery rooms should be arranged for COVID person under investigation (PUI). During delivery, a minimal number of experienced staff attending delivery should don personal protective equipment (PPE) and follow the neonatal resuscitation program (NRP). Positive pressure ventilation is best used in a negative pressure room if available. At-risk babies should be transported in an isolette, and tested for COVID-19 in a negative pressure room soon after bathing. Skin-to-skin contact and breast milk feed should continue under certain circumstances. Although newborns with COVID-19 infections often present with symptoms that mimic sepsis and one third of affected patients may demand some form of respiratory support, short-term prognoses are favorable and most recover within two weeks of symptoms onset. In this article, we will further elaborate on topics covering timing and mode of delivery, antenatal steroid, vertical transmission, delivery room management, airway management, transport, testing and isolation after birth, skin-to-skin contact, breast milk feeding, clinical features, outcomes, and discharge plans. In addition, we also share our experiences of encountering neonates born of suspected COVID-19 positive mothers., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background: Identifying preterm infants with a higher likelihood of spontaneous patent ductus arteriosus (PDA) closure would be desirable. This study aimed to examine daily PDA status during the first week of life for very low birthweight (VLBW, <1500 g) preterm infants and to develop a scoring system to predict spontaneous PDA closure., Methods: We enrolled VLBW infants admitted between January 2016 and January 2017 and performed daily echocardiographic screening for PDA existence. Oxygen index (OI, mean airway pressure × fraction of inspired oxygen/partial pressure of arterial oxygen) was applied to represent the respiratory condition., Results: A total of 215 VLBW infants were enrolled, and the accumulative incidence of spontaneous PDA closure by age 1 week was 80%, 70%, and 34% for infants born of gestational age (GA) ≥30, 28-29, and ≤27 weeks, respectively. Of these 215 infants, 184 infants entered the second phase to establish the scoring system. Infants with spontaneous PDA closure were more mature (GA 29.2 ± 2.3 vs. 26.9 ± 2.3 weeks, p < 0.001), had lower OI (2.8 ± 2.2 vs. 5.6 ± 5.3, p < 0.001) and were less likely to need endotracheal intubation (23% vs. 68%, p < 0.001). Using the receiver operating characteristics curve, OI <2.5 was determined favoring higher PDA closure incidence. The score was calculated based on the odds ratio generated in multiple regression: 4, 3 and 1 points for GA ≥30, 28-29 and ≤27 weeks, 2 and 1 points for OI <2.5 and ≥2.5, and 3 and 1 points for without and with endotracheal intubation. Using score ≥6 to predict PDA closure, the sensitivity and specificity were 0.77 and 0.72., Conclusion: A score made up of GA, OI and need for intubation was proposed to predict spontaneous PDA closure by age 1 week, which could be helpful to clinicians in the management of PDA in preterm infants., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021. Published by Elsevier B.V.)

Bacteria and fungi secrete many natural products that inhibit each other's growth and development. The dynamic changes in secreted metabolites that occur during interactions between bacteria and fungi are complicated. Pyochelin is a siderophore produced by many Pseudomonas and Burkholderia species that induces systemic resistance in plants and has been identified as an antifungal agent. Through imaging mass spectrometry and metabolomics analysis, we found that Phellinus noxius, a plant pathogen, can modify pyochelin and ent-pyochelin to an esterification product, resulting in reduced iron-chelation and loss of antifungal activity. We also observed that dehydroergosterol peroxide, the fungal metabolite, is only accumulated in the presence of pyochelin produced through bacteria-fungi interactions. For the first time, we show the fungal transformation of pyochelin in the microbial interaction. Our findings highlight the importance of understanding the dynamic changes of metabolites in microbial interactions and their influences on microbial communities.

Empedopeptins-eight amino acid cyclic lipopeptides-are calcium-dependent antibiotics that act against Gram-positive bacteria such as Staphylococcus aureus by inhibiting cell wall biosynthesis. However, to date, the biosynthetic mechanism of the empedopeptins has not been well identified. Through comparative genomics and metabolomics analysis, we identified empedopeptin and its new analogs from a marine bacterium, Massilia sp. YMA4. We then unveiled the empedopeptin biosynthetic gene cluster. The core nonribosomal peptide gene null-mutant strains (Δ empC , Δ empD , and Δ empE ) could not produce empedopeptin, while dioxygenase gene null-mutant strains (Δ empA and Δ empB ) produced several unique empedopeptin analogs. However, the antibiotic activity of Δ empA and Δ empB was significantly reduced compared with the wild-type, demonstrating that the hydroxylated amino acid residues of empedopeptin and its analogs are important to their antibiotic activity. Furthermore, we found seven bacterial strains that could produce empedopeptin-like cyclic lipopeptides using a genome mining approach. In summary, this study demonstrated that an integrated omics strategy can facilitate the discovery of potential bioactive metabolites from microbial sources without further isolation and purification.

Potato common scab, which is caused by soil-borne Streptomyces species, is a severe plant disease that results in a significant reduction in the economic value of potatoes worldwide. Due to the lack of efficacious pesticides, crop rotations, and resistant potato cultivars against the disease, we investigated whether biological control can serve as an alternative approach. In this study, multiple Bacillus species were isolated from healthy potato tubers, and Bacillus amyloliquefaciens Ba01 was chosen for further analyses based on its potency against the potato common scab pathogen Streptomyces scabies. Ba01 inhibited the growth and sporulation of S. scabies and secreted secondary metabolites such as surfactin, iturin A, and fengycin with potential activity against S. scabies as determined by imaging mass spectrometry. In pot assays, the disease severity of potato common scab decreased from 55.6 ± 11.1% (inoculated with S. scabies only) to 4.2 ± 1.4% (inoculated with S. scabies and Ba01). In the field trial, the disease severity of potato common scab was reduced from 14.4 ± 2.9% (naturally occurring) to 5.6 ± 1.1% after Ba01 treatment, representing evidence that Bacillus species control potato common scab in nature.

Carcinoma of the anal canal is a relatively rare cancer with a low propensity for metastasis. A literature review identifies two cases of brain metastases from anal cancer. The authors present the case of a 63-year-old female with poorly differentiated squamous cell carcinoma of the anal canal who presented with a solitary dural-based enhancing lesion of the right parietal area. The patient underwent craniectomy and tumor resection. Histopathology confirmed the cerebral lesion to be a poorly differentiated squamous cell carcinoma, consistent with the known primary tumor of the anal canal. Although exceptionally rare, the presence of a cerebral lesion in a patient with carcinoma of the anal canal should raise the possibility of metastatic disease. Treatment decisions in patients with newly diagnosed dural-based enhancing lesions and known anal cancer should bear in mind the possibility of metastatic disease.

Object: The Subdural Evacuating Port System (SEPS) was recently introduced as a novel method of treating chronic subdural hematomas (SDHs). This system is a variation of the existing twist-drill craniostomy methods for treating chronic SDH. Compared with craniotomy or bur hole treatment of chronic SDH, this system offers the possibility of treatment at bedside without general anesthesia. In comparison with existing twist-drill methods, the system theoretically offers the advantage of a hermetically closed system that can evacuate a hematoma without an intracranial catheter., Methods: The authors performed a case-control study of all chronic SDHs treated at a single institution over a 5-year period and compared the efficacy and safety of the SEPS to bur hole evacuation. Patients were matched for age, injury mechanism, medical comorbidities, use of anticoagulation, and radiographic appearance of the SDH. The primary outcome of interest was the recurrence rate in each group, which was evaluated by radiographic evidence as well as the number of patients requiring a second procedure. Secondary outcomes examined were mortality, infection, acute hematoma formation, seizure, length of hospital stay, length of intensive care unit stay, and discharge location., Results: The authors found that there were no appreciable differences in symptoms on presentation, existing comorbidities, home medications, or laboratory values between the treatment groups. The average Hounsfield units of preoperative CT scanning was similar in both groups. Radiographic recurrence was statistically similar between the SEPS group (25.9%) and the bur hole group (18.5%; p = 0.37). Although there was a trend toward higher reoperation rates in the SEPS group, the need for a subsequent procedure was also statistically similar between the SEPS group (25.9%) and the bur hole group (14.8%; p = 0.25). The mortality rate was not significantly different between the SEPS group (9.5%) and the bur hole group (4.8%; p = 0.50). The SEPS procedure provided a mean reduction in SDH thickness of 27.3% compared with 37.9% with bur hole (p = 0.05) when comparing the preoperative CT scan with the first postoperative CT scan. The percentage of reduction in SDH thickness when comparing the preoperative CT scan with the most recent postoperative CT scan was 40.5% in the SEPS group and 45.4% in the bur hole group (p = 0.31)., Conclusions: The SEPS offers an alternative type of twist-drill craniostomy for the treatment of chronic SDH with a trend toward higher recurrence in our experience. The efficacy and safety of SEPS is similar to that of other twist-drill methods reported in the literature. In the authors' experience, the efficacy of this treatment as measured by radiographic worsening or the need for a subsequent procedure is statistically similar to that of bur hole treatment. There was no difference in mortality or other adverse outcomes associated with SEPS.