A Mycobacterium avium subsp. paratuberculosis relA deletion mutant and a 35 kDa major membrane protein elicit development of cytotoxic T lymphocytes with ability to kill intracellular bacteria.

Efforts to develop live attenuated vaccines against Mycobacterium avium subspecies paratuberculosis (Map), using indirect methods to screen Map deletion mutants for potential efficacy, have not been successful. A reduction in the capacity to survive in macrophages has not predicted the ability of mutants to survive in vivo. Previous studies for screening of three deletion mutants in cattle and goats revealed one mutant, with a deletion in relA (ΔMap/relA), could not establish a persistent infection. Further studies, using antigen presenting cells (APC), blood dendritic cells and monocyte derived DC, pulsed with ΔMap/relA or a 35 kDa Map membrane protein (MMP) revealed a component of the response to ΔMap/relA was directed towards MMP. As reported herein, we developed a bacterium viability assay and cell culture assays for analysis and evaluation of cytotoxic T cells generated against ΔMap/relA or MMP. Analysis of the effector activity of responding cells revealed the reason ΔMap/relA could not establish a persistent infection was that vaccination elicited development of cytotoxic CD8 T cells (CTL) with the capacity to kill intracellular bacteria. We demonstrated the same CTL response could be elicited with two rounds of antigenic stimulation of APC pulsed with ΔMap/relA or MMP ex vivo. Cytotoxicity was mediated through the perforin granzyme B pathway. Finally, cognate recognition of peptides presented in context of MHC I and II molecules to CD4 and CD8 T cells is required for development of CTL.

RNA interference of carboxyesterases causes nymph mortality in the Asian citrus psyllid, Diaphorina citri.

Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), is an important pest of citrus. In addition, D. citri is the vector of Huanglongbing, a destructive disease in citrus, also known as citrus greening disease caused by Candidatus Liberibacter asiaticus. Huanglongbing causes huge losses for citrus industries. Insecticide application for D. citri is the major strategy to prevent disease spread. The heavy use of insecticides causes development of insecticide resistance. We used RNA interference (RNAi) to silence genes implicated in pesticide resistance in order to increase the susceptibility. The activity of dsRNA to reduce the expression of carboxyesterases including esterases FE4 (EstFE4) and acetylcholinesterases (AChe) in D. citri was investigated. The dsRNA was applied topically to the fourth and fifth instars of nymphs. We targeted several EstFE4 and AChe genes using dsRNA against a consensus sequence for each of them. Five concentrations (25, 50, 75, 100, 125 ng/µl) from both dsRNAs were used. The treatments with the dsRNA caused concentration dependent nymph mortality. The highest gene expression levels of both AChe and EstFE4 were found in the fourth and fifth nymphal instars. Gene expression analysis showed that AChe genes were downregulated in emerged adults from dsRNA-AChe-treated nymphs compared to controls. However, EstFE4 genes were not affected. In the same manner, treatment with dsRNA-EstFE4 reduced expression level of EstFE4 genes in emerged adults from treated nymphs, but did not affect the expression of AChe genes. In the era of environmentally friendly control strategies, RNAi is a new promising venue to reduce pesticide applications.

RNA interference of acetylcholinesterase in the Asian citrus psyllid, Diaphorina citri, increases its susceptibility to carbamate and organophosphate insecticides.

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Lividae) transmits the Candidatus Liberibacter asiaticus, which causes citrus greening disease or Huanglongbing, (HLB). To date, there is no efficient cure for HLB disease and the control of D. citri using insecticides became the most important tools for the management of HLB. However, the extensive use of insecticides could increase D. citri resistance to these insecticides. The objective of this study was to investigate the effect of RNA interference of acetylcholinesterase (AChE) on the mortality and susceptibility of D. citri to the four major insecticides used in Florida. In this study, we used a consensus sequence derived from the two AChE genes and cholinesterase 2-like (ChE-2-like) gene to target all of the three genes. Treatment with dsRNA-AChE increased the mortality percentages of both nymphs and adults of D. citri. The mortality percentage increased with the increase in the concentration of applied dsRNA-AChE, and the highest mortality (> 60%) was observed at the highest applied concentration (125ng/µl). Treatments of nymphs or adults with dsRNA-AChE down-regulated the expression of the three targeted genes of D. citri. Silencing of AChE and ChE in D. citri nymphs increased the susceptibility of emerged adults to chlorpyrifos and carbaryl, which act as AChE inhibitors. However, treatment with dsRNA-AChE did not increase the susceptibility of emerged adults to imidacloprid, which acts as an agonist of nicotinic acetylcholine receptors. In the same manner, treatment of adults with dsRNA-AChE increased their susceptibility to chlorpyrifos and carbaryl, but did not affect their susceptibility to imidacloprid. The ANOVA did not show any significant increase in susceptibility of D. citri adults to fenpropathrin after treatment with dsRNA-AChE, either as nymphs or as adults. However, simple linear regression showed that treatment with dsRNA-AChE increased D. citri susceptibility to fenpropathrin, which indicated that AChE could be involved in the metabolism of fenpropathrin. Our results indicated that silencing of AChE and ChE genes in D. citri to increase its susceptibility to insecticides could be a promising tool for the control of this important vector.

Non-viral gene delivery systems: hurdles for bench-to-bedside transformation.

Biologist and Nobel Prize winner James Watson's quote, "We used to think that our fate was in our stars, but now we know that, in large measure, our fate is in our genes", represents the initial food for thought that revolutionized the way medications and active pharmaceutical ingredients are defined (Rocholl 1996). This fate engraved in the genetic material, as mentioned in Watson's quote, fueled a tremendous revolution wave in gene therapy. Gene therapy is a promising technology for treating genetic and acquired diseases by modulating the expression of a specific gene in the pathological cells. This is achieved by introducing a DNA sequence or other nucleic acid material or oligonucleotides to the target cell (Kay, 2011). Moreover, gene therapy contributes to correction of genetic defects, expression of therapeutic proteins, and inhibition of the synthesis of malignant proteins. In this review article, different non-viral gene delivery systems and their applications are discussed in detail. We reviewed and tabulated over 90 papers and 50 patents from 2006 to date discussing non-viral gene delivery technologies, innovation, and bench-to-bedside transformation. Furthermore, we are going to shed light on the lack of standardization in the design and characterization of non-viral gene delivery systems worldwide, which is a major concern in this research's field. This review would aid in getting an eagle eye view through non-viral gene delivery technologies during the past 20 years. Such a view, capturing the advances, the hurdles, and experimental details, would aid expert researchers in tuning their experimentation strategies and help newcomers better initially design their studies to generate solid and comprehensive results that can be reliable and reproducible.

Electrical, optical, and electrochemical performances of phosphate-glasses-doped with ZnO and CuO and their composite with polyaniline.

Phosphate-based glasses (PBG) with appropriate doping agents have been used as solid electrolytes in solid-state ionic devices. Therefore, more light was shed on the electrical, optical, and electrochemical behavior of the phosphate-based glasses (PBG), containing ZnO or CuO in the absence and existence of conductive polyaniline (PANI), since no publications are available concerning this work. The glass samples were prepared by the rapid quenching method, then mixing phosphate glass and polyaniline (PANI) with metal oxide (ZnO, CuO). They were characterized by different techniques; diffuse reflectance spectrophotometer (DRS), broadband dielectric spectrometer (BDS), cyclic voltammetry (CV), and charge-discharge techniques. In the DRS study, the direct and indirect band gap were calculated from Tauc's relationship where CuO-doped glasses have higher values than ZnO-doped glasses. In the BDS study, the permittivity of all glass compositions decreased while AC conductivity increased with increasing frequency. AC conductivity of PBG doped with metal oxides and mixed with PANI exhibited semiconducting features (6.8 × 10-4 S/cm). Further, these composites exhibited lower loss tangent (0.11), and giant permittivity (186,000) compared to the pure PBG. Also, the electrochemical study exhibited that the composite with 7% CuO content has the highest specific capacitance value (82.3 F/g at 1.0 A/g) which increased to about 113% of its first cycle and then decreased to about 55% after 2500 cycles and finally increased again to 77% after 4500 cycles, indicating its good stability. The combination of optical, electrical, and electrochemical features of these composites suggests their use for energy generation and storage devices.

Generative Artificial Intelligence as a Tool for Teaching Communication in Nutrition and Dietetics Education-A Novel Education Innovation.

Although effective communication is fundamental to nutrition and dietetics practice, providing novice practitioners with efficacious training remains a challenge. Traditionally, human simulated patients have been utilised in health professions training, however their use and development can be cost and time prohibitive. Presented here is a platform the authors have created that allows students to interact with virtual simulated patients to practise and develop their communication skills. Leveraging the structured incorporation of large language models, it is designed by pedagogical content experts and comprises individual cases based on curricula and student needs. It is targeted towards the practice of rapport building, asking of difficult questions, paraphrasing and mistake making, all of which are essential to learning. Students appreciate the individualised and immediate feedback based on validated communication tools that encourage self-reflection and improvement. Early trials have shown students are enthusiastic about this platform, however further investigations are required to determine its impact as an experiential communication skills tool. This platform harnesses the power of artificial intelligence to bridge the gap between theory and practice in communication skills training, requiring significantly reduced costs and resources than traditional simulated patient encounters.

Decompressive craniectomy to cranioplasty: a retrospective observational study using Hospital Episode Statistics in England.

Objectives: To investigate the longitudinal trends of decompressive craniectomy (DC) following traumatic brain injury (TBI) or stroke and explore whether the timing of cranial reconstruction affected revision or removal rates using Hospital Episode Statistics (HES) between 2014 and 2019. Design: Retrospective observational cohort study using HES. The time frame definitions mirror those often used in clinical practice. Setting: HES data from neurosurgical centres in England. Participants: HES data related to decompressive craniectomy procedures and cranioplasty following TBI or stroke between 2014 and 2019. Main outcome measures: The primary outcome was the timing and rate of revision/removal compared with cranioplasty within <12 weeks to ≥12 weeks. Results: There were 4627 DC procedures, of which 1847 (40%) were due to head injury, 1116 (24%) were due to stroke, 728 (16%) were due to other cerebrovascular diagnoses, 317 (7%) had mixed diagnosis and 619 (13%) had no pre-specified diagnoses. The number of DC procedures performed per year ranged from 876 in 2014-2015 to 967 in 2018-2019. There were 4466 cranioplasty procedures, with 309 (7%) revisions and/or removals during the first postoperative year. There was a 33% increase in the overall number of cranioplasty procedures performed within 12 weeks, and there were 1823 patients who underwent both craniectomy and cranioplasty during the study period, with 1436 (79%) having a cranioplasty within 1 year. However, relating to the timing of cranial reconstruction, there was no evidence of any difference in the rate of revision or removal surgery in the early timing group (6.5%) compared with standard care (7.9%) (adjusted HR 0.93, 95% CIs 0.61 to 1.43; p=0.75). Conclusions: Overall number of craniectomies and the subsequent requirements for cranioplasty increased steadily during the study period. However, relating to the timing of cranial reconstruction, there was no evidence of an overall difference in the rate of revision or removal surgery in the early timing group.

Alveolar Oral Layer Repair by Periosteal Grafts versus Maxillary Flaps and Gingivoperiosteoplasty: Techniques and Follow-up to Adolescence.

Background: Alveolar periosteoplasty during primary repair of cleft lip is still a topic of debate due to the fear exacerbating maxillary retrusion. The authors present their experience with early closure of alveolar clefts. The study aims to analyze gingivoperiosteoplasty (GPP) by comparing the use of locoregional flaps versus distant grafts for reconstruction of the lower layer of the primary palate cleft. Methods: Seventeen infants underwent 22 alveolar cleft repairs. After nasal floor repair by nasal mucoperiosteum, the oral layer was repaired by maxillary or gingival periosteal flaps in seven patients with alveolar clefts less than or equal to 6 mm wide, and tibial or pericranial periosteal grafts in 10 patients with wider clefts. At teenage years, crossbites in three flap-GPP and three graft-GPP patients were compared with nine older adolescents without primary GPP. Results: Alveolar clefts were perfectly sealed. Radiographs during the early 3 postoperative years showed new bone formation more posteriorly extended in patients who underwent graft-GPP. Teeth eruption and alveolar rigidity at the mixed dentition age eliminated the need for secondary bone grafting. The anterior crossbites in adolescent patients ranged between -2 and -14 mm; crossing was relatively smaller in patients with a younger age and without cleft palate. The mean crossbite was 7.2 mm in the six teenagers and 9.6 mm in the control cases. Conclusions: Graft-GPP may be a good alternative to flap-GPP, particularly for wide alveolar cleft repair. Maxillary retrusion is aggravated in patients with cleft palate and older age at assessment. GPP may not increase crossbite.

Generation of polarization-entangled photon pairs in a Bragg reflection waveguide.

We demonstrate experimentally that spontaneous parametric down-conversion in an AlxGa(1-x)As semiconductor Bragg reflection waveguide can make for paired photons highly entangled in the polarization degree of freedom at the telecommunication wavelength of 1550 nm. The pairs of photons show visibility higher than 90% in several polarization bases and violate a Clauser-Horne-Shimony-Holt Bell-like inequality by more than 3 standard deviations. This represents a significant step toward the realization of efficient and versatile self pumped sources of entangled photon pairs on-chip.

Towards a core outcome set for cranioplasty following traumatic brain injury and stroke 'A systematic review of reported outcomes'.

Background: There is wide-ranging published literature around cranioplasty following traumatic brain injury (TBI) and stroke, but the heterogeneity of outcomes limits the ability for meta-analysis. Consensus on appropriate outcome measures has not been reached, and given the clinical and research interest, a core outcome set (COS) would be beneficial. Objectives: To collate outcomes currently reported across the cranioplasty literature which will subsequently be used in developing a cranioplasty COS. Methods: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. All full-text English studies with more than ten patients (prospective) or more than 20 patients (retrospective) published after 1990 examining outcomes in CP were eligible for inclusion. Results: The review included 205 studies from which 202 verbatim outcomes were extracted, grouped into 52 domains, and categorised into one or more of the OMERACT 2.0 framework core area(s). The total numbers of studies that reported outcomes in the core areas are 192 (94%) pathophysiological manifestations/ 114 (56%) resource use/economic impact/ 94 (46%) life impact/mortality 20 (10%). In addition, there are 61 outcome measures used in the 205 studies across all domains. Conclusion: This study shows considerable heterogeneity in the types of outcomes used across the cranioplasty literature, demonstrating the importance and necessity of developing a COS to help standardise reporting across the literature.

Isolation and Molecular Characterization of Corynebacterium pseudotuberculosis: Association with Proinflammatory Cytokines in Caseous Lymphadenitis Pyogranulomas.

Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a causative agent of numerous chronic diseases, including caseous lymphadenitis (CLA) in sheep and goats, which has a zoonotic potential in humans in addition to a poor therapeutic response. In this study, out of 120 collected samples, only 12 (10%) were positive for C. pseudotuberculosis by PCR and by intraperitoneal injection of male Guinea pigs and then characterized for antimicrobial susceptibility and its genetic-relatedness by enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR), which showed 2-4 bands ranging from 100 to 3000 bp that can be clustered into four clusters (C1-C4). Despite the serotype biovar 1 only infecting sheep and goats, ERIC-PCR reveals intra-subtyping variation. Examination of affected LNs and organs revealed marked enlargement with either thick creamy green pus or multiple abscesses of variable sizes with a central caseated core surrounded by dense fibrous capsule. A histopathological examination revealed a central necrotic core surrounded by a peripheral mantle of mononuclear cells and a fibrous capsule. Positive immune expression of nuclear factor kappa B (NF-κB/p65) and interleukin-1ß (IL-1ß) and negative expression of tumor necrosis factor (TNF) in CLA is the first report to our knowledge. Conclusion: In CLA pyogranulomas, IL1ß is a more crucial proinflammatory cytokine than TNF in the regulation of C. pseudotuberculosis infection, which is accompanied by marked NF-κB immunoexpression. Therefore, the NF-κB/p65 signaling pathway is involved in the activation of IL1ß, and additional immunohistochemical studies are required to determine the various roles of NF-κB/p65 in the inflammatory response within CLA pyogranulomas to control this pathogen.

Monolithic source of photon pairs.

The creation of monolithically integratable sources of single and entangled photons is a top research priority with formidable challenges: The production, manipulation, and measurement of the photons should all occur in the same material platform, thereby fostering stability and scalability. Here we demonstrate efficient photon pair production in a semiconductor platform, gallium arsenide. Our results show type-I spontaneous parametric down-conversion of laser light from a 2.2 mm long Bragg-reflection waveguide, and we estimate its internal pair production efficiency to be 2.0×10(-8) (pairs/pump photon). This is the first time that significant pair production has been demonstrated in a structure that can be electrically self-pumped and which can form the basis for passive optical circuitry, bringing us markedly closer to complete integration of quantum optical technologies.

Radio-opacity of commonly consumed bony fish in kelantan, malaysia.

Fish is one of the major sources of protein among Malaysians. This has made incidents of fish bones lodged in the throat fairly common clinical problems. Plain radiograph, which is the first line of imaging in such cases, has been reported to have low sensitivity. Besides the location, the degree of radio-opacity of the bone is another important factor and is species dependent. This study was undertaken to determine the radio-opacity of bones from commonly consumed fish in Malaysia. A total of 15 types of fish were identified, six of them were opaque even when embedded and three were visualized in the simulated airway. In terms of radio-opacity, the commonly consumed fish in Malaysia possessed opaque bones and this fact can help doctors identify the location of the foreign body in the throat.

Meta-analysis of the outcomes of Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) for inguinal hernia.

OBJECTIVES: To evaluate the outcomes of Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) in patients undergoing elective inguinal hernia repair. METHODS: In compliance with PRISMA statement standards, electronic databases were searched to identify all studies reporting the outcomes of TREPP in patients undergoing elective inguinal hernia repair. The outcomes of interest included recurrence, chronic pain, haematoma, and wound infection. Proportion meta-analysis model was constructed to quantify the risk of postoperative complications and direct comparison meta-analysis model was constructed to compare the outcomes of TREPP and other open techniques. Random-effects modelling was applied to calculate pooled outcome data. RESULTS: Seven studies enrolling 1891 patients undergoing TREPP were included. The mean operative time was 26 min (95% CI 15-36). Pooled analyses showed that TREPP was associated with 3.00% (95% CI 1.00-6.00%) risk of recurrence, 3.00% (95% CI 2.00-6.00%) risk of chronic pain, 8.00% (95% CI 0.00-20.00%) risk of haematoma, and 3.00% (95% CI 0.00-6.00%) risk of wound infection. The results remained consistent through subgroup analysis of patients with primary hernias and those with recurrent hernias. Analysis of a limited number of comparative studies showed no difference between TREPP and Lichtenstein technique in terms of recurrence (OR 1.57, P = 0.26) and chronic pain (OR 1.16, P = 0.59). CONCLUSIONS: The best available evidence suggests that TREPP may be a promising technique for elective repair of inguinal hernias as indicated by low risks of recurrence, chronic pain, haematoma, and wound infection. The available evidence is limited to studies from a same country conducted by almost the same research group which may affect generalisability of the findings. Moreover, there is a lack of comparative evidence on outcomes of TREPP versus other techniques highlighting a need for high-quality randomised controlled trials for definite conclusions. Although the available evidence is not adequate for definite conclusions, the results of current study can be used for sample size calculation and power analysis in future trials.

Cranioplasty: A Multidisciplinary Approach.

Decompressive craniectomy (DC) is an operation where a large section of the skull is removed to accommodate brain swelling. Patients who survive will usually require subsequent reconstruction of the skull using either their own bone or an artificial prosthesis, known as cranioplasty. Cranioplasty restores skull integrity but can also improve neurological function. Standard care following DC consists of the performance of cranioplasty several months later as historically, there was a concern that earlier cranioplasty may increase the risk of infection. However, recent systematic reviews have challenged this and have demonstrated that an early cranioplasty (within three months after DC) may enhance neurological recovery. However, patients are often transferred to a rehabilitation unit following their acute index admission and before their cranioplasty. A better understanding of the pathophysiological effects of cranioplasty and the relationship of timing and complications would enable more focused patient tailored rehabilitation programs, thus maximizing the benefit following cranioplasty. This may maximise recovery potential, possibly resulting in improved functional and cognitive gains, enhancement of quality of life and potentially reducing longer-term care needs. This narrative review aims to update multi-disciplinary team regarding cranioplasty, including its history, pathophysiological consequences on recovery, complications, and important clinical considerations both in the acute and rehabilitation settings.

Efficacy of the topical cyclosporine cream assisted by fractional carbon dioxide laser vs topical clobetasol cream for the treatment of plaque psoriasis: Randomized comparative study.

BACKGROUND: In mild psoriasis, topical agents remain the mainstay of treatment. However, the available treatments are not satisfactory for a significant proportion of patients in many terms such as efficacy and safety. Because of these deficits, augmentation of therapeutic effect seems desirable. THIS STUDY AIMS: To evaluate the efficacy of topical cyclosporine cream, delivered by fractional CO2 laser vs the efficacy of topical clobetasol cream for the treatment of mild to moderate plaque psoriasis. PATIENTS AND METHODS: Twenty-two patients with chronic plaque psoriasis involving <10% BSA were included in this study. They were randomly allocated into 2 groups. In Group A, patients were instructed to apply cyclosporine cream twice daily for 5 consecutive days per week immediately after fractional carbon dioxide laser session. While in Group B, clobetasol cream was applied twice daily for 5 consecutive days per week until complete clearance or for a maximum of 10 weeks. The efficacy was objectively assisted clinically and by histopathology by using the scores and skin biopsy. RESULTS: There was a significant improvement of erythema, plaque elevation, and scaling (p < 0.001) with the use of topical cyclosporine cream delivered by the aid of fractional CO2 laser, compared to base line. However, the improvement was more significant with topical clobetasol cream. CONCLUSION: Laser-assisted delivery of topical cyclosporine can provide comparable clinical and pathological improvement to that of clobetasol in the psoriatic plaques. These findings were apparent in patients with less widespread disease. However, topical steroid showed more improvement.

Evaluation of the outcome of a proposed more physiological bypass surgery technique in morbid obesity: Long term 3 years follows up.

Background: Obesity is a chronic condition that affects millions globally; consequently, bariatric surgery is the key to this serious issue. Bariatric procedures are rapidly expanding in number and methods to address the recognized problems. So, it would make a sense for surgeons and patients if there is a more physiological bypass surgery technique in Morbid obesity. This study aims to evaluate the outcome proposed technique. Patients and methods: The present study is a retrospective analysis on 256 participants subjected to the proposed bypass procedure from December 1999 to January 2017, the participants were followed up for an interval of 3years. Results: The findings of the present study revealed a significant Excess Weight Loss (EWL). In addition, patients experienced decreased calcium, iron, vitamin B12, Hemoglobin, zinc, and Prothrombin Concentration. However, three to six months after surgery, they experienced a significant improvement until they reached normal levels without any supplement by the end of 12,18 months, with a three-year follow-up. Conclusion: This proposed Bypass Operation aims to adequate digestions as well as selective absorption without inducing any vital deficit. Most of study's population showed no elements inadequacies, although few percentages emerged during the interval of maximal weight reduction, and it were transient and minimal. No minerals or vitamins were needed.

Discriminant value of serum HBV DNA levels as predictors of liver fibrosis in chronic hepatitis B.

Current guidelines recommend antiviral therapy in chronic hepatitis B (HBV) patients with significant histological disease. We aimed to compare histological fibrosis (METAVIR, ≥F2) in patients with HBV DNA ≥20,000 IU/mL vs. ≥2000 IU/mL and identify predictors of fibrosis. We performed prospective liver biopsies on 203 HBeAg-negative patients in four groups: Group I (n = 55): HBV DNA ≥20,000 IU/mL and persistently elevated alanine aminotransferase (ALT) levels (PEALT; >40 U/L); Group II (n = 34): HBV DNA ≥20,000 IU/mL and persistently normal ALT (PNALT); Group III (n = 40): HBV DNA <20,000 IU/mL and PEALT; and Group IV (n = 74): HBV DNA <20,000 IU/mL, and PNALT. We reanalysed all groups in relation to updated cut-off for treatable viremia (2000 IU/mL). Genotype D was detected in 86% of patients. Hepatic fibrosis ≥F2 was detected in 72.7%, 52.9%, 57.5% and 18.9% in Groups I-IV, respectively (P < 0.0001). Except in Group II with a trend for lower ≥F2 fibrosis (P = 0.067), there was no significant difference by using HBV DNA cut-off 20,000 vs. 2000 IU/mL. Multivariate logistic regression analysis identified study Group IV (OR, 0.0276; CI: 0.088-0.868; P = 0.0276) and milder (A0-1) necroinflammatory grade (OR, 0.135; CI: 0.063-0.287; P < 0.0001) as independent predictors of ≥F2 fibrosis. The specificity, positive and negative predictive values for PEALT in detection of ≥F2 fibrosis for viremia ≥2000 IU/mL (80%, 69% and 65%, respectively) or ≥20,000 IU/mL (86%, 73% and 63%, respectively) were similar, with a marginal gain in sensitivity (51% vs. 42%, respectively). Significant fibrosis is prevalent in a large proportion of HBeAg-negative patients with high viremia and persistently normal ALT. Lower HBV DNA cut-offs could be adopted with marginal gains in fibrosis detection and without loss of diagnostic accuracy.

Proposal for on-chip generation and control of photon hyperentanglement.

An on-chip waveguide-based source of entangled photons capable of switching between generating time-energy entangled and hyperentangled (entangled in both time energy and polarization) photon pairs is proposed. The switching can be done all-optically by rotating the pump polarization. The source is based on multichannel phase matching in Bragg reflection waveguides achieved by engineering the Fresnel reflection of photonic bandgap claddings for differently polarized modes. Analytical results are confirmed in fully vectorial numerical simulations.

Prevalence of extended-spectrum ß-lactamase (ESBL)-producing Salmonella enterica from retail fishes in Egypt: A major threat to public health.

The increase in multidrug-resistant Salmonella enterica and its spread from food to humans are considered a serious public health concern worldwide. Little is currently known about the prevalence of extended-spectrum ß-lactamase (ESBL)-producing S. enterica in fish in Africa. Therefore, this study aimed to investigate the existence of ESBL-producing S. enterica in retail fish in Egypt. In total, 200 fish samples were collected randomly from various retail fish markets in Egypt. S. enterica were detected in 19 (9.5%; 95% CI: 5.8-14.4) of the fish samples analyzed. Of the 19 non-repetitive S. enterica isolates, 18 were serologically categorized into eight S. enterica serovars and a non-typable serovar. All 19 S. enterica isolates (100%) showed multidrug-resistant phenotypes to at least three classes of antimicrobials, and 11 (57.9%) exhibited an ESBL-resistant phenotype and harbored at least one ESBL-encoding gene. The ESBL-producing S. enterica serovars were as follows: Kentucky (3 isolates; 15.8%), Enteritidis (2 isolates; 10.5%), Typhimurium (2 isolates; 10.5%), and 1 isolate (5.3%) each of Infantis, Virchow, Paratyphi B, and Senftenberg. The identified ß-lactamase-encoding genes included ESBL-encoding genes blaCTX-M-3, blaCTX-M-14, blaCTX-M-15, blaSHV-1, blaSHV-2 and blaSHV-12; the AmpC ß-lactamase-encoding gene blaCMY-2; and the narrow-spectrum ß-lactamase-encoding genes blaTEM-1 and blaOXA-1. All S. enterica isolates were negative for carbapenemase-encoding genes. Molecular analysis of plasmid transferability and replicon typing revealed that most plasmids (with ß-lactamase-encoding genes) were transferrable, and the most common incompatibility groups were IncI1, IncA/C, IncHI1, and IncN. To the best of our knowledge, this is the first report for molecular characterization of ESBL-producing S. enterica in fish in Egypt. The occurrence of ESBL-producing S. enterica in retail fish constitutes a potential public health threat with the possibility of transmission of these strains with resistance genes to humans. Such transmission would exacerbate the resistance to an important class of antibiotics commonly used in hospitals to treat typhoid and non-typhoidal Salmonella infections.