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Introduction: The conjunctiva contains numerous specialized cells called conjunctival goblet cells (CGCs). The topical application of specific eye drops to the ocular surface has conclusively been linked to cause a reduction in CGCs, a condition which has been associated with dry eye and other ocular surface disorders. The purpose of this study was to assess if the use of benzalkonium chloride (BAK) as a preservative in common ophthalmic medications affects CGCs' density in New Zealand white (NZW) rabbit conjunctivas.

Methods: Data from seven preclinical studies conducted between March 2016 and April 2021 were analyzed, involving 146 male NZW rabbits aged 2 to 3 months. Prior to study participation, rabbits underwent a 7-day quarantine period in individual housing, during which their general health was monitored. Rabbits had ad libitum access to water and food, with intake data recorded. Comprehensive ophthalmological examinations were performed on all eyes prior to and throughout the studies. The density of corneal endothelial cells was specifically assessed using AB/PAS staining and quantified with a high-power (40X) field objective (ocular 18 × 22), expressed as a percentage relative to epithelial cells.

Results: No statistically significant differences were found between the with-BAK group and without-BAK group. The mean density in the 30-day group presented a statistically significant higher density than the >30-day group (p = 0.005). Analysis of the treatment revealed that antibiotic/steroid combination group had a higher average number of CGCs compared to both the antihistaminic group (p = 0.004) and hypotensive agent group (p = 0.047).

Conclusion: Exposure to BAK-preserved medications for 30 days results in a higher density of CGCs compared to prolonged exposure to BAK-preserved medications exceeding 30 days. The pharmacological effects and associated cellular damage induced by BAK vary depending on the specific medication with which it is combined.

Introduction: Central diabetes insipidus (CDI) is a rare disorder caused by a deficiency in the secretion of arginine vasopressin (AVP) from the posterior pituitary. It can be either acquired or congenital, often due to genetic factors, and is typically inherited in an autosomal dominant manner.

Case presentation: This study describes the clinical features and the genetic analysis of a father and his son with familial CDI. Both presented in childhood with typical symptoms, including polyuria, polydipsia, and hypernatremia. Diagnosis was confirmed through water deprivation testing and subsequently supported by sellar magnetic resonance imaging. Genetic analysis identified the rare germline variant c.329G>A (p.Cys110Tyr) in the AVP gene, in heterozygosity, which segregated in the parent-child pair, thereby elucidating the familial basis of the CDI.

Conclusion: This rare germline AVP variant causes a cysteine-to-tyrosine amino acid substitution in the encoded protein and is classified as pathogenic. Familial cases of rare diseases, such as CDI, highlight the importance of clinical evaluation of relatives with similar symptoms and emphasize the need for molecular studies and genetic counseling.

Introduction: Calciphylaxis is a rare and severe disorder characterized by obstructive small vessel disease in the subcutaneous adipose tissue and skin, leading to necrotic skin lesions. The condition poses a significant risk of mortality due to infectious and ischemic complications.

Case presentation: We present the case of a 60-year-old woman, with a history of renal lithiasis, hypertension, and end-stage renal disease on hemodialysis complicated by hyperparathyroidism and aortic valve replacement. She developed extensive necrotic lesions on both lower limbs and upper extremities, prompting a diagnosis of calciphylaxis. Radiographic and biopsy findings supported the diagnosis, revealing characteristic calcifications. Treatment involved antibiotics, oral thiosulfate, daily hemodialysis, hyperbaric oxygen therapy, and discontinuation of calcium and alfacalcidol, with alendronate initiation. Unfortunately, despite these interventions, the patient experienced a rapid clinical decline, developing septic shock necessitating bilateral leg amputations. Regrettably, she succumbed to the disease 10 days later.

Conclusion: This case underscores the challenging prognosis of calciphylaxis and the need for effective therapeutic options, including surgical intervention and access to injectable thiosulfate.

Introduction: In acute ischaemic stroke, the key treatment to reduce infarct growth is reperfusion, achieved through thrombolysis, endovascular thrombectomy, or endogenous reperfusion. Prior to definitive reperfusion therapy, blood pressure augmentation may enhance cerebral perfusion and reduce interim infarct growth. This study aimed to summarise the existing evidence from randomised controlled trials on the use of imaging for patient selection and the assessment of blood pressure augmentation in acute ischaemic stroke.

Methods: A systematic review was conducted of the databases PubMed, Embase, and Cochrane Library in accordance with the PRISMA guidelines. The systematic review was prospectively registered on PROSPERO.

Results: Initial searches returned 266 results, of which 4 fulfilled inclusion criteria. Most identified studies did not utilise imaging for patient selection and the assessment of blood pressure augmentation in ischaemic stroke. Only two studies utilised magnetic resonance imaging and/or magnetic resonance perfusion imaging for patient selection, while one study used non-contrast CT brain. No studies utilised CT perfusion imaging for patient selection or outcome assessment post-blood pressure augmentation. There is also a lack of evidence regarding the association between specific perfusion imaging parameters, such as cerebral blood volume and delay time, and clinical outcomes post-blood pressure augmentation.

Conclusion: Imaging is a potentially valuable surrogate marker of cerebral perfusion, yet it has not been routinely used for patient selection and assessment in blood pressure augmentation in acute ischaemic stroke trials. Additional research is required to determine its utility in assessing the efficacy of blood pressure augmentation in ischaemic stroke.

Introduction: Vitiligo, a skin disorder affecting melanocytes, poses treatment challenges. There is a need to investigate the role of tacrolimus in pediatric cases for its efficacy and safety. The present study aimed to assess the safety and efficacy of tacrolimus ointment in treating pediatric vitiligo patients.

Methods: A review study was conducted, and a literature search was done on 2 August 2023, by using the words "vitiligo" and "tacrolimus" through five databases including PubMed. We found 8 studies from 930 records.

Results: The rates of excellent, moderate, mild, minimal improvement, and no response were 29% (95% CI: 16-47), 26% (95% CI: 19-35), 28% (95% CI: 20-37), 19% (95% CI: 12-29), and 8% (95% CI: 2-25). No systemic side effects were reported. The overall prevalence of local side effects was 14% (95% CI: 7-24). Burning sensation prevalence was 11% (95% CI: 7-18), while pruritus prevalence was 9% (95% CI: 2-33). Study limitations encompassed varied vitiligo sites, patient demographics, and follow-up durations, lacked comparative treatment data, and necessitated further research on combined therapies, especially in pediatric cases.

Conclusion: Tacrolimus showed good efficacy regarding the re-pigmentation improvement in pediatric vitiligo patients. Furthermore, no systemic side effects were reported and local side effects were minimal mainly in the form of a burning sensation and pruritus.

Introduction: Monogenic diseases can be diagnosed before birth. Systemic fetal administration of nanoparticles (NPs) grants therapeutic access to developing stem cell populations impacted by these classes of disease. Delivery of editing reagents in these NPs administered before birth has yielded encouraging results in preclinical mouse models of monogenic diseases.

Methods: To translate this strategy clinically, the safety and efficacy of this strategy in larger animals will be necessary. We performed a pilot biodistribution study in 3 fetal nonhuman primates (NHPs) in mid-gestation examining systemic delivery of polymeric NPs loaded with fluorescent dye.

Results: We found several similarities in distribution to our experience in mice, namely, extensive uptake in fetal liver and spleen. A striking finding that is not recapitulated in the mouse was the accumulation of NPs in the zones of proliferation and ossification of the fetal bone. Of great importance, there did not appear to be NP accumulation in the fetal male or female germline zones or maternal tissue.

Conclusion: These studies were vital to the next step of testing editing reagents in the fetal NHP with a goal of treating monogenic diseases before birth.

Introduction: The factors influencing meconium aspiration syndrome (MAS) severity remain poorly understood. In a piglet model of MAS, we hypothesized the respiratory microbiome would reflect the bacterial signature of meconium with short-chain fatty acid (SCFA) accumulation as a byproduct of bacterial fermentation.

Methods: Cesarean section at approximately 115-day term was performed on two sows. Male (9) and female (3) piglets were delivered, instrumented, anesthetized, and randomized into a Control (n = 6) or MAS group (n = 6). MAS received a meconium slurry (3 mL/kg) aspiration injury. Experimental animals were monitored continuously, ventilated, and resuscitated for 24 h. BALF was collected for 16S microbiome sequencing and SCFA analysis by gas chromatography. Effects of SCFAs on A549 alveolar pulmonary epithelial in vitro cell viability and inflammation were assessed.

Results: The MAS group had significantly higher fluid and vasopressor requirements than the Control group (p < 0.05) though both groups developed lung injury. The meconium microbiome demonstrated a difference in genus proportions as compared with the BALF of the Control and MAS groups. The MAS group had a relative increase in propionic acid-forming bacteria and higher BALF concentrations of propionic acid (0.6 ± 0.2 mmol/kg) than the Control group (0.2 ± 0.2 mmol/kg; p > 0.05). Propionic acid was associated with decreased pulmonary epithelial cell viability and an upregulated pro-inflammatory response.

Conclusions: Meconium may host a microbiome with byproducts that interact with the pulmonary epithelium and influence lung injury severity in MAS.

Introduction: Transposition of the great arteries (TGA), especially with intact ventricular septum (TGA-IVS), presents unique challenges during fetal-to-neonatal transition, which can contribute to developing persistent pulmonary hypertension of the newborn (PPHN).

Case presentation: A male newborn with TGA-IVS, delivered via caesarean section, presented with hypoxemia and tachycardia immediately after birth (preductal SpO₂: 50-60%, post-ductal SpO₂: 70-75%). Echocardiography revealed a floppy interatrial septum and two interatrial connections with bidirectional shunting. Ductal flow showed systolic right-to-left shunting, suggesting high pulmonary vascular resistance. Immediate post-birth management included non-invasive respiratory support with continuous positive airway pressure at 100% oxygen and administration of prostaglandin E2 to maintain ductal patency. Despite initial low oxygen saturation levels, escalation of intensive treatments was deferred based on continuous trend monitoring of vital signs and echocardiographic indicators. Oxygenation and circulation gradually improved within the first 2 h after birth to normal values, obviating escalation of intensive interventions like intubation, nitric oxide and/or balloon atrial septostomy. Arterial switch operation at day 3 post-birth was successful.

Conclusion: This case highlights the possible contribution of fetal-to-neonatal transition in TGA-IVS to developing PPHN, which may subside after transition. Moreover, this case highlights the potential for providing a gentle hemodynamic transition without invariably needing early invasive interventions after birth.

Introduction: Peritonitis is a significant complication of peritoneal dialysis (PD). Additionally, in severe or prolonged cases of peritonitis, the structure and function of the peritoneum may change, making it difficult to continue PD. Thus, identifying the causative agent and early administration of antibiotics are essential to minimize the risk of treatment failure. Meanwhile, bacterial peritonitis caused by nontuberculous Mycobacteria (NTM) are difficult to identify. NTM are also among the most difficult organisms to eradicate. Oftentimes, removal of the peritoneal catheter and multiple antibiotics are required to eradicate NTM infections.

Case presentation: Herein, we report a case of peritonitis caused by Mycobacterium fortuitum in a 3-year-old boy undergoing PD. The patient had a history of an initial PD catheter exit site infection caused by M. fortuitum that led to PD-associated peritonitis. Consequently, the catheter was removed, and the patient was switched to hemodialysis and treated with multiple antibiotics.

Conclusion: This rare cause of peritonitis is associated with a high mortality and severe morbidity and usually requires removal of the PD catheter as well as prolonged treatment with multiple antibiotics. When there is NTM infection around the PD catheter, such as in an ulcer, it is necessary to remove the catheter and transition to a hemodialysis until the infection has healed.

Introduction: Knowing an individualized outcome prediction is essential when counseling patients before surgery. We aim to identify predictors and build a model for the outcome of radiofrequency uvulopalatopharyngoplasty with tonsillectomy (rfUPPP + TE).

Methods: All adult patients undergoing rfUPPP + TE for sleep-disordered breathing from 2015 to 2022 in our institution were included. Preoperative evaluations included detailed upper airway examinations and standardized questionnaires. Postoperative outcomes were measured through home sleep apnea testing and repeated questionnaires 3 months post-surgery. The primary endpoint was the postoperative apnea-hypopnea index (AHI) and the AHI responders using the Sher criteria.

Results: We analyzed 247 patients with a mean age of 46 ± 11 years, predominantly male (88.7%), and a mean BMI of 29.0 kg/m². The mean AHI was reduced from 26.4 ± 18.6/h preoperatively to 16.2 ± 14.6/h postoperatively. Daytime sleepiness improved from 8.9 ± 48 to 4.0 ± 3.1 and snoring from 7.9 ± 2.1 to 3.3 ± 2.2. Multivariate analysis indicated that higher tonsil grades, preoperative AHI, and snoring levels were associated with a greater reduction in AHI. Age and body weight were negative predictors for AHI reduction. For AHI responders, according to Sher, tonsil grade was the only predictor in a multivariate analysis. The ROC curve of this simple model, with a corrected AUC of 0.625, compared favorably against two established models.

Conclusion: Our study highlights that tonsil grade, preoperative AHI, snoring, and, to a smaller extent, age and weight are key determinants of AHI reduction, emphasizing the importance of preoperative evaluation. Despite the multifactorial nature of obstructive sleep apnea, preoperative evaluation can predict the outcome of rfUPPP + TE and guide surgical planning.