Antibiotic choice for the management of preterm premature rupture of membranes in Taiwanese women.

BACKGROUND: Preterm premature rupture of membranes (PPROM) is one of the most common causes of preterm birth. Antibiotic treatment is recommended to prolong the pregnancy course and reduce fetal morbidity in women with PPROM. However, the guidelines for antibiotic selection are based on studies done years ago, mostly in Western countries, which may not reflect the geographic, temporal, and ethnic variation in microbial colonization and infection in other parts of the world. We aimed to understand whether the antibiotics recommended by the current guidelines were sufficient to eradicate the majority of pathogens involved. METHODS: This is a single-center retrospective study at a tertiary medical center in Taiwan with patients recruited from January 1, 2017, to December 31, 2019. All patient included had a confirmed diagnosis of PPROM. In this study, we aimed to investigate which broad-spectrum antibiotic was most suitable for PPROM cases in Taiwan. RESULTS: 133 women were included, and 121 women had positive culture results. Most of the pregnant women had one positive result (35.5%). The most common pathogen was Lactobacillus species (27.8%), followed by Streptococcus species (12.9%) and Staphylococcus species (12.09%). CONCLUSION: The most appropriate antibiotic therapy for PPROM was a combination of 1 g azithromycin given orally on admission plus a third-generation cephalosporin administered intravenously in the first 48 hours and followed by amoxicillin 500 mg per os for another five days. This recommended antibiotic regimen for women with PPROM needs further study under a randomized clinical trial with a larger study population to evaluate its efficacy.

Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications.

Mesenchymal stem/stromal cells (MSCs) are a promising resource for cell-based therapy because of their high immunomodulation ability, tropism towards inflamed and injured tissues, and their easy access and isolation. Currently, there are more than 1200 registered MSC clinical trials globally. However, a lack of standardized methods to characterize cell safety, efficacy, and biodistribution dramatically hinders the progress of MSC utility in clinical practice. In this review, we summarize the current state of MSC-based cell therapy, focusing on the systemic safety and biodistribution of MSCs. MSC-associated risks of tumor initiation and promotion and the underlying mechanisms of these risks are discussed. In addition, MSC biodistribution methodology and the pharmacokinetics and pharmacodynamics of cell therapies are addressed. Better understanding of the systemic safety and biodistribution of MSCs will facilitate future clinical applications of precision medicine using stem cells.

Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies.

Endometriosis is an estrogen-dependent inflammatory disease that affects up to 10% of women of reproductive age and accounts for up to 50% of female infertility cases. It has been highly associated with poorer outcomes of assisted reproductive technology (ART), including decreased oocyte retrieval, lower implantation, and pregnancy rates. A better understanding of the pathogenesis of endometriosis-associated infertility is crucial for improving infertility treatment outcomes. Current theories regarding how endometriosis reduces fertility include anatomical distortion, ovulatory dysfunction, and niche inflammation-associated peritoneal or implantation defects. This review will survey the latest evidence on the role of inflammatory niche in the peritoneal cavity, ovaries, and uterus of endometriosis patients. Nonhormone treatment strategies that target these inflammation processes are also included. Furthermore, mesenchymal stem cell-based therapies are highlighted for potential endometriosis treatment because of their immunomodulatory effects and tropism toward inflamed lesion foci. Potential applications of stem cell therapy in treatment of endometriosis-associated infertility in particular for safety and efficacy are discussed.

Gliomatosis cerebri with spinal metastasis presenting with chronic meningitis in two boys.

Spinal cord involvement in gliomatosis cerebri (GC) is uncommon. We report two patients with GC, who initially presented with chronic meningitis and were treated with antituberculous drugs. Although tumor meningitis was suspected, due to the intractable clinical course, a correct diagnosis was established after performing a biopsy examination of the metastatic spinal lesion which was detected by magnetic resonance imaging (MRI). Cerebrospinal fluid examination, including cytology, should be performed repetitively for patients with chronic meningitis refractory to antibiotic treatment. Spinal MRI is necessary for the complete neurological workup, even when the patients do not show spinal symptoms.

Fertility and Pregnancy Outcomes after Fertility-Sparing Surgery for Early-Stage Borderline Ovarian Tumors and Epithelial Ovarian Cancer: A Single-Center Study.

This study examined treatment outcomes, including preserved fertility, menstrual regularity, and pregnancy outcomes, in patients with stage I epithelial ovarian cancer (EOC) or borderline ovarian tumors (BOTs) who underwent fertility-sparing surgery (FSS). Patients with stage I EOC and BOTs who were aged 18-45 years and underwent FSS between 2007 and 2022 were retrospectively reviewed. Significant differences between various subgroups in terms of disease recurrence, menstrual irregularity due to the disease, and pregnancy outcomes were analyzed. A total of 71 patients with BOTs and 33 patients with EOC were included. In the BOT group, the median age was 30 (range, 19-44) years. Recurrence occurred in eight patients, with one case exhibiting a malignant transformation into mucinous EOC. Among the 35 married patients with BOTs, 20 successfully conceived, resulting in 23 live births and 3 spontaneous abortions. A higher pregnancy rate was observed in those without prior childbirth (82.4%) than in those who had prior childbirth (33.3%). In the EOC group, the median age was 34 (range, 22-42) years. Recurrence occurred in one patient. Menstrual regularity was maintained in 69.7% of the patients. Among the 14 married patients in this group, 12 achieved a total of 15 pregnancies (including 2 twin pregnancies), 16 live births, and 1 spontaneous abortion. The results of the study confirmed that FSS is a favorable surgical option for young women with early-stage BOTs or EOC who wish to preserve their fertility. However, additional investigations are needed to validate these findings.

A rare cause of childhood-onset nephrotic syndrome: lipoprotein glomerulopathy.

We report on a 12-year-old female patient with lipoprotein glomerulopathy (LPG) who was proven to be heterozygous for ApoE2 Kyoto (Arg25Cys). Her family members have the same variant but do not have obvious signs of renal function impairment. Six months of treatment with a statin caused significant clinical improvement in the lipid profile, proteinuria, and renal function. Our case suggests that administration of a statin is a potential therapeutic strategy for improving nephrotic syndrome in patients with LPG.

A high resolution time-to-digital-convertor based on a carry-chain and DSP48E1 adders in a 28-nm field-programmable-gate-array.

A field-programmable-gate-array (FPGA) based time-to-digital-converter (TDC), which combines different types of delay chains in a single time measurement channel, is reported in this paper. A new TDC architecture is developed, and both a carry-chain and the DSP48E1 adders, which are integrated inside the FPGA chip, are employed to achieve high resolution time tagging. A single channel TDC has a 3.3 ps averaged bin size, a 5.4 ps single-shot precision, and a maximum sampling rate of 250 MSa/s. The differential-non-linearity of the single TDC channel is -3.3 ps/+24.1 ps, and the integral-non-linearity is within -10.4 ps/+68.6 ps. The TDC performance can be improved by using four TDC channels to measure one input signal, and a 3.4 ps single-shot precision can be obtained. Due to the implementation of the delicated TDC structure, only a small amount of digital resources is required to achieve the picosecond time measurement resolution. Therefore, the reported TDC architecture is suitable for multi-channel applications that require high time resolution measurements of multiple input signals.

Calreticulin promotes EMT in pancreatic cancer via mediating Ca2+ dependent acute and chronic endoplasmic reticulum stress.

BACKGROUND: Our previous study showed that calreticulin (CRT) promoted EGF-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) via Integrin/EGFR-ERK/MAPK signaling. We next investigated the novel signal pathway and molecular mechanism involving the oncogenic role of CRT in PC. METHODS: We investigated the potential role and mechanism of CRT in regulating intracellular free Ca2+ dependent acute and chronic endoplasmic reticulum stress (ERS)-induced EMT in PC in vitro and vivo. RESULTS: Thapsigargin (TG) induced acute ERS via increasing intracellular free Ca2+ in PC cells, which was reversed by CRT silencing. Additionally, CRT silencing inhibited TG-induced EMT in vitro by reversing TG-induced changes of the key proteins in EMT signaling (ZO-1, E-cadherin and Slug) and ERK/MAPK signaling (pERK). TG-promoted cell invasion and migration was also rescued by CRT silencing but enhanced by IRE1α silencing (one of the key stressors in unfolded protein response). Meanwhile, CRT was co-immunoprecipitated and co-localized with IRE1α in vitro and its silencing led to the chronic ERS via upregulating IRE1α independent of IRE1-XBP1 axis. Moreover, CRT silencing inhibited IRE1α silencing-promoted EMT, including inhibiting the activation of EMT and ERK/MAPK signaling and the promotion of cell mobility. In vivo, CRT silencing decreased subcutaneous tumor size and distant liver metastasis following with the increase of IRE1α expression. A negative relationship between CRT and IRE1α was also observed in clinical PC samples, which coordinately promoted the advanced clinical stages and poor prognosis of PC patients. CONCLUSIONS: CRT promotes EMT in PC via mediating intracellular free Ca2+ dependent TG-induced acute ERS and IRE1α-mediated chronic ERS via Slug and ERK/MAPK signaling.

Limited effects of antibiotic prophylaxis in patients with Child-Pugh class A/B cirrhosis and upper gastrointestinal bleeding.

Current guidelines recommend antibiotic prophylaxis for all patients with various degrees of cirrhosis and upper gastrointestinal (UGI) bleeding. This study assessed the need for antibiotic prophylaxis in patients with low Child-Pugh scores. We retrospectively screened all patients with cirrhosis who underwent upper endoscopies for UGI bleeding in a referral hospital in Taiwan between 2003 and 2014, from which 913 patients were enrolled after excluding patients with active bacterial infections, recent antibiotic use, early death, and Child-Pugh class C cirrhosis. Among them, 73 (8%) received prophylactic antibiotics, and 45 (4.9%) exhibited 14-day bacterial infection. Neither Child-Pugh score nor model for end stage liver disease score were optimal for predicting bacterial infection because their areas under the curves were 0.610 (95% confidence interval [CI]: 0.529-0.691) and 0.666 (95% CI: 0.591-0.742), respectively. Antibiotic prophylaxis did not reduce the risks of 14-day bacterial infection (relative risk [RR]: 0.932, 95% CI: 0.300-2.891, P = 0.902), 14-day rebleeding (RR: 0.791, 95% CI: 0.287-2.181, P = 0.650), or 42-day mortality (RR: 2.710, 95% CI: 0.769-9.524, P = 0.121). The results remained similar after propensity score adjustment. On-demand antibiotic treatment might suffice for patients with Child-Pugh class A/B cirrhosis and UGI bleeding.

One to chelate them all: investigation of a versatile, bifunctional chelator for 64Cu, 99mTc, Re and Co.

We describe the synthesis of the dip (di-picolyl-carboxylate) bifunctional chelator system, capable of fast coordination of Cu(2+), (64)Cu(2+) and Co(2+), as well as the [M(CO)(3)](+)-core (M = (99m)Tc, Re); it displays a variety of binding modes--tridentate when protected, tetradentate when deprotected. Syntheses of both the benzyl-nitro derivative and the benzyl-amino derivatives are described. The latter was coupled to biotin to show the viability of the system for functionalization with biomolecules. Besides coordination chemistry with stable isotopes, we also present labelling data with (64)Cu and (99m)Tc, as well as in vitro stability studies.