Neutrophils and monocyte toll like receptors 2 and 4 expression in preterm versus term delivery.

Pregnancy results in an increase in immune cells, especially monocytes, which enhances the innate immune system. The increase of inflammatory cytokines in pregnant women's amniotic fluid, can cause uterine contraction, is linked to preterm labor. These inflammatory responses are controlled by Toll-like receptors (TLRs), which are largely expressed on neutrophils and monocytes. This study aimed to determine the role of neutrophils and monocyte subsets, as well as their expression of TLR-2 and TLR-4 in women with preterm and full-term delivery. The study involved a total of 74 women, comprising of 29 preterm labor, 25 full-term labor, and 20 non-pregnant women. The distribution of three monocyte subsets, namely (CD14++CD16-), (CD14+CD16+), and (CD14-/dim CD16++) was measured. Also, the expression of TLR2 and TLR4 in monocytes and neutrophils was analyzed using flow cytometry. Non-classical monocytes and intermediate monocytes were significantly higher in the preterm group than the control and full-term groups (p=0.041, p=0.043, and p=0.004, p= 0.049, respectively). Women in the preterm group showed significantly TLR2 expression on nonclassical monocytes compared to the control and full-term groups (p=0.002, and p=0.010, respectively). Also, preterm group expression of TLR4 was significantly higher in classical monocytes and nonclassical monocytes in comparison to the control group (p=0.019, and p≤0.0001, respectively). Besides, TLR4 expression was significantly up regulated in the preterm group compared to full-term in non-classical monocyte subset (p < 0.0001). Moreover, the expression of TLR-4 in neutrophils from the preterm group was statistically higher than expression from the full-term labor and control groups (p < .0001 for both). Such findings highlight the important role of monocyte subsets and neutrophils in activating the innate immune system and initiating strong pro-inflammatory responses that induce preterm labor. Additionally, TLR4 and TLR2 expressions on non-classical monocytes may be used as a marker to assess the probability of preterm labor.

Effects of mesenchymal stem cells versus curcumin on sonic hedgehog signaling in experimental model of Hepatocellular Carcinoma.

BACKGROUND: Sonic Hedgehog (SHH) is a fundamental signaling pathway that controls tissue reconstruction, stem cell biology, and differentiation and has a role in gut tissue homeostasis and development. Dysregulation of SHH leads to the development of HCC. METHODS, AND RESULTS: The present study was conducted to compare the effects of mesenchymal stem cells (MSCs) and curcumin on SHH molecular targets in an experimental model of HCC in rats. One hundred rats were divided equally into the following groups: control group, HCC group, HCC group received MSCs, HCC group received curcumin, and HCC group received MSCs and curcumin. Histopathological examinations were performed, and gene expression of SHH signaling target genes (SHH, PTCH1, SMOH, and GLI1) was assessed by real-time PCR in rat liver tissue. Results showed that SHH target genes were significantly upregulated in HCC-untreated rat groups and in MSC-treated groups, with no significant difference between them. Administration of curcumin with or without combined administration of MSCs led to a significant down-regulation of SHH target genes, with no significant differences between both groups. As regards the histopathological examination of liver tissues, both curcumin and MSCs, either through separate use or their combined use, led to a significant restoration of normal liver pathology. CONCLUSIONS: In conclusion, SHH signaling is upregulated in the HCC experimental model. MSCs do not inhibit the upregulated SHH target genes in HCC. Curcumin use with or without MSCs administration led to a significant down-regulation of SHH signaling in HCC and a significant restoration of normal liver pathology.

Prevalence of Chronic Middle Ear Effusion in Cases of Cleft Palate.

Chronic middle ear effusion is generally present in children with cleft palate (CP) associated with or without cleft lips. The aim of our study was to assessment of how common middle ear effusion is in patients with cleft palates and to evaluate the presence of these symptoms by performing a Basic Audiological Evaluation (BAE). A retrospective randomized study was conducted on 50 children (29 male and 21 female) aged 2 to 16 years who had CPs (associated with or without cleft lips) with symptoms of middle ear effusion. The study was conducted from March 2021 to February 2022. Data review included the results of otoscopic findings and BAE. The Fundamentals of BAE comprise the testing of middle ear function with tympanometry and a pure tone audiometry to determine the kind and degree of hearing impairment. Regarding the BAE, we found that 70% of the children with normal hearing, 24% with conductive type of hearing loss, and 6% with mixed type of hearing loss. The tympanometric results revealed that 66% of the children with type A tympanogram, 24% with type C tympanogram, and 10% with type B tympanogram. The contralateral stapedial reflex was present in 60% of the patients while in 40% of cases not present. The results confirmed the great prevalence of chronic middle ear effusion in children with CPs. Furthermore, the hearing impairment associated with middle ear effusion was visible, demonstrating that middle ear effusion was linked with the prevalence of moderate conductive type of hearing loss. The OME in cases of CP necessitates early prediction and in turn early treatment.

Role of Loupes Magnification in Tracheal Resection and Anastomosis.

Tracheal resection and anastomosis is characterized in the last years by significant innovations which are well codified and standardized. Although the mortality rate is markedly reduced, the operation is still not free from risk of complications such as recurrent laryngeal nerve injury, anastomosis dehiscence, granulation tissue formation and restenosis. Pearson FG, Cooper ID, Nelems JL (1975) Primary tracheal anastomosis after resection of the cricoide cartilage with preservation of the recurrent laryngeal nerves. J Thorac Cardiovasc Surg 70:806-16. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04115-3.

Dopaminergic and prefrontal dynamics co-determine mouse decisions in a spatial gambling task.

The neural mechanisms by which animals initiate goal-directed actions, choose between options, or explore opportunities remain unknown. Here, we develop a spatial gambling task in which mice, to obtain intracranial self-stimulation rewards, self-determine the initiation, direction, vigor, and pace of their actions based on their knowledge of the outcomes. Using electrophysiological recordings, pharmacology, and optogenetics, we identify a sequence of oscillations and firings in the ventral tegmental area (VTA), orbitofrontal cortex (OFC), and prefrontal cortex (PFC) that co-encodes and co-determines self-initiation and choices. This sequence appeared with learning as an uncued realignment of spontaneous dynamics. Interactions between the structures varied with the reward context, particularly the uncertainty associated with the different options. We suggest that self-generated choices arise from a distributed circuit based on an OFC-VTA core determining whether to wait for or initiate actions, while the PFC is specifically engaged by reward uncertainty in action selection and pace.

Clitoral Therapy Device for Alleviating Sexual Dysfunction After Female Genital Mutilation: Randomized Controlled Trial.

BACKGROUND: Female genital mutilation is considered a crime but is still practiced today in Africa and the Middle East, despite all the laws that make this procedure illegal due to the long-term physical and psychological harm it causes to women. Millions of girls and women living today have undergone genital mutilation, which involves removing the external female genitalia either partially or totally, based on the belief that it restricts feminine sexuality, thereby "saving" a girl for marriage. For girls and women, the surgery offers no health advantages. Girls' right to control critical decisions regarding their sexual and reproductive health is violated because genital mutilation is frequently done against their will and frequently without their consent, leading to lifelong psychic trauma in addition to sexual dysfunction and lack of satisfaction due to distortion of the genitalia that threatens marital stability. OBJECTIVE: To determine the effect of a clitoral therapy device on improving sexual domains in women suffering from sexual dysfunction after female genital mutilation. METHODS: This study examined 80 married women aged from 20 to 45 years who were referred from the gynecology outpatient clinic of the Faculty of Medicine, Suez University, for sexual dysfunction resulting from female genital mutilation. The women were divided into 2 equal groups: the study group received a clitoral therapy device and traditional psychosexual education and were closely followed for 3 months, while the control group received only traditional psychosexual education for 3 months. The Arabic version of the Female Sexual Function Index (FSFI) questionnaire was used to assess sexual outcomes pre- and posttreatment in the 2 groups. RESULTS: Our findings revealed a significant increase in the 6 domains of the FSFI pretreatment in both groups compared to posttreatment (P>.001), except the orgasm domain in the control group, which showed only a nonsignificant increase (P=.16). CONCLUSIONS: Clitoral therapy devices may be an effective, safe, noninvasive rehabilitation method for sexual dysfunction following female genital mutilation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05039775; https://clinicaltrials.gov/ct2/show/NCT05039775.

A Biodegradable Bioactive Glass-Based Hydration Sensor for Biomedical Applications.

Monitoring changes in edema-associated intracranial pressure that complicates trauma or surgery would lead to improved outcomes. Implantable pressure sensors have been explored, but these sensors require post-surgical removal, leading to the risk of injury to brain tissue. The use of biodegradable implantable sensors would help to eliminate this risk. Here, we demonstrate a bioactive glass (BaG)-based hydration sensor. Fluorine (CaF2) containing BaG (BaG-F) was produced by adding 5, 10 or 20 wt.% of CaF2 to a BaG matrix using a melting manufacturing technique. The structure, morphology and electrical properties of the resulting constructs were evaluated to understand the physical and electrical behaviors of this BaG-based sensor. Synthesis process for the production of the BaG-F-based sensor was validated by assessing the structural and electrical properties. The structure was observed to be amorphous and dense, the porosity decreased and grain size increased with increasing CaF2 content in the BaG matrix. We demonstrated that this BaG-F chemical composition is highly sensitive to hydration, and that the electrical sensitivity (resistive-capacitive) is induced by hydration and reversed by dehydration. These properties make BaG-F suitable for use as a humidity sensor to monitor brain edema and, consequently, provide an alert for increased intracranial pressure.

Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases).

OBJECTIVES: To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases. METHODS: The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019. RESULTS: Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued. CONCLUSION: These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.

Comparative Study of Measurement Methods for Embedded Bioimpedance Spectroscopy Systems.

Bioimpedance spectroscopy (BIS) is an advanced measurement method for providing information on impedance changes at several frequencies by injecting a low current into a device under test and analyzing the response voltage. Several methods have been elaborated for BIS measurement, calculating impedance with a gain phase detector (GPD), IQ demodulation, and fast Fourier transform (FFT). Although the measurement method has a big influence on the measurement system performance, a systematical comparative study has not been performed yet. In this paper, we compare them based on simulations and experimental studies. To maintain similar conditions in the implementation of all methods, we use the same signal generator followed by a voltage-controlled current source (VCCS) as a signal generator. For performance analysis, three DUTs have been designed to imitate the typical behavior of biological tissues. A laboratory impedance analyzer is used as a reference. The comparison addresses magnitude measurement accuracy, phase measurement accuracy, signal processing, hardware complexity, and power consumption. The result shows that the FFT-based system excels with high accuracy for amplitude and phase measurement while providing the lowest hardware complexity, and power consumption, but it needs a much higher software complexity.

Endoscopic third ventriculostomy for the management of hydrocephalus secondary to posterior fossa tumors: A retrospective study.

BACKGROUND: Endoscopic third ventriculostomy (ETV) is an effective alternative to ventriculoperitoneal shunting as well as external ventricular drainage for the urgent management of acute hydrocephalus. We performed this study to investigate the efficacy and safety of ETV before tumor resection in managing hydrocephalus in patients with posterior fossa brain tumors (PFBT) in our neurosurgery department. METHODS: We conducted this retrospective observational study between February 2018 and February 2020 on all cases diagnosed with PFBT associated with triventricular obstructive hydrocephalus. We retrospectively reviewed the demographic characteristics, operative procedures, and radiological investigations of all cases. During the follow-up period, clinical, as well as radiological success were evaluated. RESULTS: Twenty-two ETV procedures were performed in 22 cases of PFBT (mean age = 22.1 years, SD = 11.4). Of the 22 cases, 8 cases (36.4%) had ependymoma, 7 cases (31.8%) had cerebellar astrocytoma, and 5 cases (22.7 %) had medulloblastoma, while 2 cases (9.1%) had diffuse pontine gliomas. The median follow-up duration was 9 months (range 3-13 months). The most commonly reported clinical presentation was the significant intracranial pressure increase. All operations were performed successfully in all cases. Only two ETV post-tumor resection failures were documented during the follow-up period. CONCLUSION: Preoperative ETV has shown to be an effective long-term cerebrospinal fluid diversion procedure to manage PFBT-associated hydrocephalus, with a relatively low rate of complications. Further prospective studies are required to assess the regular use of ETV before complete tumor resection.

Periodontal diseases and potential risk factors in Egyptian adult population-Results from a national cross-sectional study.

BACKGROUND: Despite the interdependence of general and periodontal health, there is paucity of national representative data on the prevalence of periodontal diseases and their associated risk factors in Egyptian population. This cross-sectional study, thus, aimed to assess the prevalence of periodontitis and tooth loss among Egyptian adults and investigate the association between potential risk factors and periodontal diseases. METHODS: A total of 5,954 adults aged ≥ 20 years were included in this study as a subsample from Egypt's national oral health survey. Periodontitis was diagnosed with Community Periodontal Index 'CPI' scores ≥3 and tooth loss not due to caries was included in the analysis. Socio-demographic data and information on behavioral factors and history of diabetes were gathered in a face-to-face interview. Logistic regression was done to interpret the impact of potential predictors on the incidence of the two selected outcome variables. RESULTS: The overall prevalence of periodontitis was 26% and regression analysis revealed that higher odds of periodontitis existed among illiterate participants (OR = 1.74; 95% CI: 1.40-2.17), smokers (OR = 1.93; 95% CI: 1.69-2.20) and rural residents (OR = 1.16; 95% CI: 1.03-1.30). On the other hand, old age, frequency of dental attendance and history of diabetes were the main predictive factors for tooth loss. CONCLUSIONS: Among Egyptian adults, periodontal diseases were strongly associated with a multitude of modifiable and non-modifiable risk factors and inequalities in distribution of periodontal treatment needs were determined mainly by age, gender, level of education and residency location.

Chronic nicotine increases midbrain dopamine neuron activity and biases individual strategies towards reduced exploration in mice.

Long-term exposure to nicotine alters brain circuits and induces profound changes in decision-making strategies, affecting behaviors both related and unrelated to drug seeking and consumption. Using an intracranial self-stimulation reward-based foraging task, we investigated in mice the impact of chronic nicotine on midbrain dopamine neuron activity and its consequence on the trade-off between exploitation and exploration. Model-based and archetypal analysis revealed substantial inter-individual variability in decision-making strategies, with mice passively exposed to nicotine shifting toward a more exploitative profile compared to non-exposed animals. We then mimicked the effect of chronic nicotine on the tonic activity of dopamine neurons using optogenetics, and found that photo-stimulated mice adopted a behavioral phenotype similar to that of mice exposed to chronic nicotine. Our results reveal a key role of tonic midbrain dopamine in the exploration/exploitation trade-off and highlight a potential mechanism by which nicotine affects the exploration/exploitation balance and decision-making.

The effect of anemia on the efficacy and safety of treating chronic hepatitis C infection with direct-acting antivirals in patients with chronic kidney disease.

BACKGROUND/AIM: Chronic hepatitis-C infection is a great health burden in Egypt. The effect of anemia on the efficacy and safety of direct-acting anti-viral (DAA) therapies for those with chronic-kidney disease (CKD) has not been evaluated. PATIENTS/METHODS: This single-center retrospective study included 235 renal patients: i.e., 70-CKD patients not on hemodialysis (42 with anemia, 28 without); 40 hemodialysis patients (16 anemic; 24 non-anemic), and 125 kidney-transplant (KTx) recipients (40 anemic; 85 non-anemic). Anemia was defined by a hemoglobin level < 10.5 g/dL. Hemodialysis patients received ritonavir-boosted paritaprevir/ombitasvir. KTx patients received sofosbuvir/daclatasvir. CKD patients with eGFR > 30 mL/min/1.73 m2 received sofosbuvir/daclatasvir. Those with eGFR < 30 mL/min/1.73 m2 received ritonavir-boosted paritaprevir/ombitasvir; 64 non-anemic patients also received ribavirin therapy. RESULTS: Mean age of CKDs was 49.1 years, 43.2 years for HDs, and 45.2 years for KTx patients. Most were male; body-mass index was ~ 23.8. Anemia did not affect the efficacy of DAAs in hemodialysis, CKD, or KTx patients. Most patients achieved a rapid virologic response (RVR), and a 12- and 24-week sustained viral response. Worsening of anemia among the non-anemic group was mostly related to ribavirin therapy in hemodialysis patients (11/16 patients). Acute kidney injury in CKDs occurred more frequently within the anemic group (59.5%) compared to the non-anemic group (32.1%). For KTx, graft impairment was more common among the anemic group (7/40) compared to the non-anemic group (2/85). CONCLUSION: Hemoglobin levels of < 10.5 g/dL prior to DAA treatment did not affect the virological response in renal patients but was associated with increased serum creatinine among KTx and those with CKD.

Treatment of Brucellosis in Guinea Pigs via a Combination of Engineered Novel pH-Responsive Curcumin Niosome Hydrogel and Doxycycline-Loaded Chitosan-Sodium Alginate Nanoparticles: an In Vitro and In Vivo Study.

Brucellosis is a common zoonotic infection, particularly in the developing world. The recommended treatment regimens for brucellosis involve the use of two medications such as doxycycline and curcumin in order to avoid relapses and prolonged use of these drugs. Doxycycline has excellent activity in the acidic phagolysosomal environment, while curcumin modulates the immune system function and macrophage activity. Due to the intracellular existence of Brucellae and the different anti-immune mechanisms of Brucella, the treatment of Brucella infection faces many limitations. The design of nanosystems is a promising treatment approach for brucellosis. The objective of this study was to design and evaluate the efficacy of in situ pH-responsive curcumin-loaded niosome hydrogel and doxycycline-loaded chitosan-sodium alginate nanoparticles as chemotherapeutic agents against brucellosis. The prepared formulae showed a spherical nano shape with a slow drug release pattern and small particle size. The prepared formulae were evaluated in vivo using Guinea pigs experimentally infected with Brucella melitensis biovar3. The prepared formula combination gave a significant high reduction rate of Brucella spleen viable count compared with that of untreated controls at p < 0.05. The results showed that the treatment schemes were not fully successful in eliminating Brucella infection in Guinea pigs; however, they significantly (p < 0.05) reduced the viable Brucella count in a shorter time and sub-therapeutic doses. Collectively the novel prepared formulae could be a successful therapy for the effective treatment of brucellosis infection at the recommended therapeutic doses. Graphical abstract.

[Tick-borne relapsing fever : An unrecognized cause of fever in travellers]. / La fièvre récurrente à tiques : une cause méconnue de fièvre du voyageur.

INTRODUCTION: Tick-borne relapsing fever is a usual cause of fever in West Africa. Except relapsing febrile episodes, there are no pathognomonic signs and diagnosis is difficult because Borrelia density in patient's blood is low. CASE REPORTS: Tick-borne relapsing fever was revealed by the presence of spirochetes in a blood sample to search malaria in two men, 24 and 31 year-old, returned from Mali. CONCLUSION: This diagnosis should be evocated in patients having fever after a trip in infested area, as malaria, both infections can be associated.

Mice adaptively generate choice variability in a deterministic task.

Can decisions be made solely by chance? Can variability be intrinsic to the decision-maker or is it inherited from environmental conditions? To investigate these questions, we designed a deterministic setting in which mice are rewarded for non-repetitive choice sequences, and modeled the experiment using reinforcement learning. We found that mice progressively increased their choice variability. Although an optimal strategy based on sequences learning was theoretically possible and would be more rewarding, animals used a pseudo-random selection which ensures high success rate. This was not the case if the animal is exposed to a uniform probabilistic reward delivery. We also show that mice were blind to changes in the temporal structure of reward delivery once they learned to choose at random. Overall, our results demonstrate that a decision-making process can self-generate variability and randomness, even when the rules governing reward delivery are neither stochastic nor volatile.

Measurement System for Lossy Capacitive Sensors: Application to Edible Oils Quality Assessment.

This paper aimed to develop a portable, low-cost, and easy-to-use measurement system for oil quality degradation assessment. The main two chemical parameters affected by frying are the total polar compounds (TPC) and free fatty acids. The system should characterize the change of chemical parameters by measuring the changes in its dielectric parameters. The dielectric parameters, relative permittivity, and conductivity are measured by measuring the capacitance and resistance of a capacitive sensor dipped in oil. The main challenges are that the corresponding changes of the capacitance and resistance are very small and the presence of stray effects. For this reason, the measurement system should be able to detect changes in capacitance and resistance with high resolution and with good immunity to stray effects. The proposed measurement system is based on the conversion of impedance to voltage and time and combining, therefore, having two measurement methods in one circuit. In this way, it is possible to measure the dielectric and resistive parameters and not only the relative permittivity as was done in previous works. The results showed a strong correlation between the chemical and electrical parameters with a coefficient of determination in the range of 0.9.

High rate of acute kidney injury in patients with chronic kidney disease and hepatitis C virus genotype 4 treated with direct-acting antiviral agents.

BACKGROUND: Direct-acting antivirals (DAAs) have significantly improved the efficacy and safety of treating chronic hepatitis C (CHC), but their effectiveness and safety among patients with chronic kidney disease (CKD) remains poorly understood. Sofosbuvir/daclatasvir regimen is supposed to be used for patients with creatinine clearance more than 30 mL/min, while ombitasvir/paritaprevir/ritonavir regimen is used for patients with creatinine clearance less than 30 mL/min. AIM: The aim of the study was to assess the safety and efficacy of DAAs among patients with CKD. METHODS: Eighteen CKD stage 2-3b patients received sofosbuvir for 3 months. In addition, 42 CKD stage-4 patients received ritonavir-boosted paritaprevir plus ombitasvir for 3 months. Finally, ribavirin was added for 30 of them. RESULTS: The patients'age was 49.2 ± 12 years. Baseline serum creatinine was 3.76 ± 1.67 mg/dL. Fifty patients were HCV genotype 4. A 3-month sustained viral response was achieved in 56 patients and 49 patients achieved a 6-month viral response. There were 11 relapsers. Acute kidney injury (AKI) upon CKD (AKI/CKD) occurred in 28 patients, of which 20 needed hemodialysis. Fifteen/28 recovered from AKI, whereas 13 were maintained on hemodialysis. In multivariate analysis, there were only two independent risk factors for developing AKI/CKD, i.e., being cirrhotic as defined by baseline abdominal ultrasound findings [odds ratio 4.15 (1.33-12.97); p = 0.013] and having had as DAA therapy OMV/PTV/RTV [odds ratio 7.35 (1.84-29.35); p = 0.001]. CONCLUSION: Treatment of HCV among stage 2, 3a, and 3b patients was achieved safely with a sofosbuvir-based regimen. We recommend that stage-4 patients wait until starting hemodialysis or transplantation.