Synergistic immunomodulatory effect of synbiotics pre- and postoperative resection of pancreatic ductal adenocarcinoma: a randomized controlled study.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a highly immunosuppressive microenvironment. This single-blind, randomized study aimed to evaluate the synergistic immunomodulatory effects of synbiotics (probiotics and inulin prebiotics), as well as their impact on postoperative complications and outcomes, compared to the use of probiotics alone. Ninety patients diagnosed with PDAC were enrolled and randomly assigned into three groups: the placebo group, the probiotics group (receiving a mixture of ten strains of Lactobacillus, Bifidobacterium, and Streptococcus bacteria at a dose of 25 billion CFUs), and the synbiotics group (the same probiotics along with inulin prebiotics). The interventions were administered for 14 days before the surgery and continued for one month postoperatively. Tumor tissue infiltration of CD8 + T cells and the expression of IFN γ were assessed by immunohistochemistry (IHC). Inflammatory cytokines concentrations, including Il 1 B, IL 6, and IL 10, were evaluated as well by ELISA at various time points pre- and postoperative. Furthermore, patients were followed up after the surgery to assess postoperative short-term outcomes. Our results showed a significant elevation of CD8 + T cell proportion and IFN γ expression in the synbiotics group compared to the probiotics group (p = 0.049, p = 0.013, respectively). Inflammatory cytokines showed a significant gradual decrease in the synbiotics group compared to placebo and probiotics-treated groups (p = 0.000 for both). Administration of synbiotics and probiotics significantly decreased the rate of postoperative complications including anastomotic leakage, diarrhea, and abdominal distension (p = 0.032, p = 0.044, p = 0.042, respectively), with a remarkable reduction in bacteremia in the synbiotics group. These results revealed that this synbiotics formulation potentially enhances the immune response and reduces complications associated with surgery.Clinical trial identification: NCT06199752 (27-12-2023).

Modified streptavidin-biotin based lateral flow test strip for rapid detection of SARS-CoV-2 S1 antigen in saliva samples.

Compared to other infectious diseases, for which LFT development can take years, SARS-CoV-2 antigen LFTS were developed and deployed within months. LFTS for antigen detection were adopted on an unprecedented scale during the COVID-19 pandemic, but many of them lack the sensitivity especially for samples with low viral load. In our previous work, we developed an enhanced signal strip for detection of SARS CoV-2 SI antigens in saliva. Here we introduce some modification to improve the sensitivity, and specificity, and to lower the cost of the strip, by using biotin streptavidin (BS) system. In the modified BS strip, gold-streptavidin and biotinylated Nanobodies (Nbs) against S1 antigen were externally mixed with the tested samples (saliva or nasopharyngeal swab) before their application on the sample pad of the test strip containing angiotensin converting enzyme (ACE-2), as the capturing probe. The study included 320 individuals, with 180 being positively confirmed by RT-PCR and 140 confirmed negative, as well as, 45 health care workers, who were responsible for screening and handling of surgical cases in General Surgery Department and COVID clinic of TBRI. Our results proved that modified BS strip improved the overall sensitivity and specificity of S1antigen detection in saliva samples (95.21% and 99.29% respectively) compared to our previously developed enhanced LFTS (91.66% and 98.57% respectively). Also, the sensitivity of cases with Ct ≤ 30, Ct ≤ 35, and Ct ≤ 40 using the modified BS strip showed higher values (98.54%, 95.38%, and 88.89% respectively), compared to the corresponding results of our previously developed enhanced LFTS (95.86%, 92.31%, and 82.22% respectively). There were no cross-reactions with either Middle East respiratory syndrome corona virus MERS-CoV or SARS-CoV antigens. Furthermore, we found that the lower viral detection limit (LVD) of BS strip was obviously lower than our previous LVD limit of the enhanced LFTS (0.2 × 104 copies/ml vs. 0.4 × 104 copies/ml, respectively). Our developed BS strip showed that saliva samples gave better results than nasopharyngeal swabs of the same patients. The fact of using smaller amounts of Nbs, and ACE2, as well as the dispensing off of conjugate pad when applying BS strip modifications, justified the expected reduction in the costs of the strip. The implementation of BS strips on saliva samples of 45 health co-workers, who were tested 4 and 6 days after exposure to infection, showed an increase in the sensitivity, starting from the 4th day and reaching its highest level on the 6th day in both high risk and paramedic groups (90.9%, and 80.0%, respectively). This study provides evidence that employment of the modified BS system could increase the sensitivity of the strips, lower their cost, and render them an effective screening tool for early detection of the virus in saliva of suspected Covid-19 patients.

Zip-up Loop Myopexy in Heavy Eye Syndrome.

PURPOSE: To describe and report the results of a zip-up modification for loop myopexy for facilitating a muscle union procedure in heavy eye syndrome. METHODS: A retrospective chart review was conducted on patients with heavy eye syndrome in whom the modified surgical technique was performed. Superior and lateral rectus muscle bellies were approximated using a suture 4 to 5 mm from the muscle insertion. Muscles were then zipped together by 5-0 polyester sutures placed in an anteroposterior direction using a hand-over-hand technique. Details of the surgical technique were reported. Ductions, versions, and angles of strabismus were evaluated before and after surgery. Complications were reported. RESULTS: A total of 8 patients were identified (mean age: 60.8 ± 7 years). Mean axial length was 33.2 ± 1.2 mm. Mean preoperative horizontal and vertical angles of deviation were 78 ± 20 prism diopters (PD) (range: 50 to 120 PD) and 34 ± 4 PD (range: 30 to 40 PD), respectively. Preoperative limitation of abduction and elevation was -4 to -5 in all patients. An average of seven to eight sutures were used. No intraoperative complications were reported. In 7 patients, both vertical and horizontal angles of deviation were reduced to within 8 PD from orthophoria and limitation of ductions was reduced to null or -1 after surgery. Undercorrection occurred in 1 patient with bilateral heavy eye syndrome who had unilateral surgery. No recurrences developed over a median of 6 months of follow-up. CONCLUSIONS: A zip-up modification for loop myopexy can facilitate the surgical procedure to achieve a satisfactory outcome in heavy eye syndrome. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].

Risk of atrial fibrillation development in adolescent patients with inflammatory bowel disease.

There is increasing evidence linking chronic inflammation to the initiation and continuation of atrial fibrillation (AF). Inflammatory bowel diseases (IBD), namely (Crohn's disease (CD) and ulcerative colitis (UC), are chronic systemic inflammatory disorders with both intestinal and extra-intestinal manifestations. Atrial electromechanical delay (EMD) has been known as an early marker of AF. The objective of this study was to evaluate the atrial electromechanical properties in children and adolescents with IBD during remission. One hundred IBD patients aged 12-17 years (50 with CD and 50 with UC) in remission state and 100 healthy controls were recruited for the study. Atrial electromechanical properties were measured using transthoracic echocardiography, tissue Doppler imaging, and simultaneous surface ECG recording. Interatrial EMD, left intra-atrial, and right intra-atrial EMD were calculated. IBD patients in remission state have significantly prolonged left and right intra-atrial EMD and interatrial EMD compared to healthy controls (P = 0.03, P = 0.02, and P = 0.01 respectively). No statistical difference was observed between CD and UC in terms of inter- and intra-atrial EMDs.  Conclusion: Atrial EMD is increased in pediatric patients with IBD indicating the increased risk of AF development. Measurement of atrial EMD parameters might be used to predict the risk of the development of AF in pediatric patients with IBD. What is Known: • There is increasing evidence linking chronic inflammation to the initiation and continuation of atrial fibrillation (AF). • Inflammatory bowel diseases are chronic systemic inflammatory disorders with both intestinal and extra-intestinal manifestations. • Atrial electromechanical delay (EMD) has been reported as an early marker of AF. What is New: • Atrial EMD is increased in pediatric patients with IBD indicating the increased risk of AF development. • Measurement of atrial EMD parameters might be used to predict the risk of the development of AF in pediatric patients with IBD.

Helicobacter pylori infection and gut microbiota in adolescents: Is there a relation?

Helicobacter pylori infection is a prevalent global infection associated with several complications such as peptic ulcer, upper gastrointestinal bleeding, and stomach cancer. An imbalance in the gut microbiota composition or the relationship between the microbiota and the host may be implicated in the infection. To investigate this, we studied the intestinal microbiota of 50 newly infected adolescents with H. pylori compared with 50 age-matched and sex-matched healthy controls. The gut microbiota composition was assessed using real-time polymerase chain reaction (RT-PCR), and the fecal bacterial diversity and composition were compared between groups. Our findings revealed that Clostridium difficile and Salmonella spp. were significantly higher in the patient group compared to the control group. Additionally, lower counts of eubacteria, Bacteroides fragilis, Lactobacillus spp., Escherichia coli, and Methanobrevibacter smithii, were observed in the gut of adolescents with H. pylori. Conversely, adolescents with H. pylori infection had non-significantly higher counts of Bifidobacterium spp., C. difficile, and Salmonella spp. Multiple logistic regression analysis revealed that a greater abundance of Bifidobacterium spp. and Salmonella spp., a higher prevalence of C. difficile, and a lower abundance of Lactobacillus spp. were predictive of H. pylori infection. Overall, our results suggest that H. pylori infection is associated with changes in fecal microbiome composition.

Gold conjugated nanobodies in a signal-enhanced lateral flow test strip for rapid detection of SARS-CoV-2 S1 antigen in saliva samples.

Despite the transfer of COVID-19 from the pandemic to control, we are still in a state of uncertainty about long-term success. Therefore, there is a great need for rapid and sensitive diagnostics to sustain the control status. After several optimization trials, we developed lateral flow test (LFT) strips for rapid detection of SARS-CoV-2 spike 1 (S1) antigen in saliva samples. For signal enhancement of our developed strips, we applied dual gold conjugates. Gold-labeled anti-S1 nanobodies (Nbs) were employed as S1 detector conjugate, while gold-labeled angiotensin-converting enzyme 2 (ACE2) was used as S1 capturing conjugate. In a parallel strip design, we used an anti-S1 monoclonal antibody (mAb) as an antigen detector instead of anti-S1 Nbs. Saliva samples were collected from 320 symptomatic subjects (180 RT-PCR confirmed positive cases and 140 confirmed negative cases) and were tested with the developed strips. In early detection for positive samples with cycle threshold (Ct ≤ 30), Nbs-based LFT strips showed higher sensitivity (97.14%) and specificity (98.57%) than mAb-based strips which gave 90.04% sensitivity and 97.86% specificity. Moreover, the limit of detection (LoD) for virus particles was lower for Nbs-based LFT (0.4 × 104 copies/ml) than for the mAb-based test (1.6 × 104 copies/ml). Our results are in favor of the use of dual gold Nbs and ACE2 conjugates in LFT strips. These signal-enhanced strips offer a sensitive diagnostic tool for rapid screening of SARS-CoV-2 S1 antigen in the easily collected saliva samples.

Torsional Changes After Vertical Transposition of Horizontal Recti in V-pattern Exotropia Without Oblique Dysfunction.

PURPOSE: To evaluate pattern collapse and torsional changes following vertical transposition of horizontal recti in patients with V-pattern exotropia and no oblique dysfunction. METHODS: A prospective study was performed on patients who had V-pattern exotropia and no oblique dysfunction. Lateral recti were transposed upward half-tendon width in V-pattern of 25 prism diopters (PD) or less (n = 14) and full-tendon width in V-pattern of greater than 25 PD (n = 10). Amblyopic patients had unilateral lateral rectus recession with upward transposition and medial rectus resection with downward transposition (n = 8). Ductions, versions, pattern strabismus, disc foveal angle, and astigmatic axis were analyzed before and 6 months after surgery. RESULTS: In the 32 patients (21 females), the mean age was 8.25 ± 1.23 years. Only amblyopic patients showed preoperative fundus extorsion (mean disc foveal angle = 16.9°, P < .01). Mean pattern collapse was 13.1 ± 3.8 PD with half-tendon transposition, 35.6 ± 13.7 PD with full-tendon transposition, and 13.8 ± 7.9 PD in the unilateral group. Pattern collapse increased gradually so that pattern normalization occurred after 6 months in most patients. There was a statistically significant correlation between the preoperative V-pattern and the magnitude of pattern collapse after surgery (r = 0.80, P < .01). There were no significant changes in the mean disc foveal angle (< 0.5°) or axis of astigmatism (< 0.5°) in all three groups. CONCLUSIONS: Vertical transposition of horizontal muscles can correct V-pattern exotropia, although the effect might not be immediate. Torsional changes are minimal. Amblyopic patients with V-pattern exotropia showed a preoperative extorsion that did not change after surgery. [J Pediatr Ophthalmol Strabismus. 2019;56(2):107-115.].

Tumor-derived CCL-2 and CXCL-8 as possible prognostic markers of breast cancer: correlation with estrogen and progestrone receptor phenotyping.

Prognosis of breast cancer is believed to be a multifactorial process best achieved by complex factors including host and tumor-derived biomarkers together with traditional clinicopathological parameters and tumor histologic markers. The present study aimed at evaluating the prognostic significance of chemokine ligand-2 (CCL-2) and interleukin-8 (CXCL-8) expression in extracts of breast carcinomas through correlation with clinicopathological aspects as well as estrogen receptor (ER) and progesterone receptor (PR) phenotyping. The study was conducted on 30 Egyptian breast cancer patients diagnosed by fine needle aspiration cytology (FNAC) and subjected to modified radical mastectomy. Excised tissues were used to prepare tissue sections and extracts for histopathological and immunohistochemical studies. Expression of CCL-2 and CXCL-8 was determined by enzyme-linked immunosorbent assay (ELISA). 26 patients had invasive ductal carcinoma, grades II and III with metastasis to axillary lymph nodes and ER and PR positive phenotype. Expression of CCL-2 and CXCL-8 was significantly influenced by patient's age, menopausal status, nodal involvement, tumor grade and the ER phenotype. In contrast, it was not affected by either tumor size or PR staining pattern. Both chemokines correlated positively to each other and to tumor grade and negatively to age, menopausal status of patients and ER phenotyping. It is concluded that the angiogenic chemokine CXCL-8 and the macrophage chemoattractant CCL-2 might be useful prognostic markers where their routine follow up might be of importance in assessment of tumor aggressiveness in clinical settings.