Period Of Latency Research Articles

Development of new real-time PCR assays for detection and species differentiation of Plasmodium ovale.

The parasite species formerly known as Plasmodium ovale, Plasmodium ovalecurtisi (P. ovalecurtisi) and Plasmodium ovalewallikeri (P. ovalewallikeri), are endemic across multiple African countries. These species are thought to differ in clinical symptomatology and latency, but only a small number of existing diagnostic assays can detect and distinguish them. In this study, we sought to develop new assays for the detection and differentiation of P. ovalecurtisi and P. ovalewallikeri by leveraging recently published whole-genome sequences for both species. Repetitive sequence motifs were identified in available P. ovalecurtisi and P. ovalewallikeri genomes and used for assay development and validation. We evaluated the analytical sensitivity of the best-performing singleplex and duplex assays using synthetic plasmids. We then evaluated the specificity of the duplex assay using a panel of samples from Tanzania and the Democratic Republic of the Congo (DRC), and validated its performance using 55 P. ovale samples and 40 non-ovale Plasmodium samples from the DRC. The best-performing P. ovalecurtisi and P. ovalewallikeri targets had 9 and 8 copies within the reference genomes, respectively. The P. ovalecurtisi assay had high sensitivity with a 95% confidence lower limit of detection (LOD) of 3.6 parasite genome equivalents/μl, while the P. ovalewallikeri assay had a 95% confidence LOD of 25.9 parasite genome equivalents/μl. A duplex assay targeting both species had 100% specificity and 95% confidence LOD of 4.2 and 41.2 parasite genome equivalents/μl for P. ovalecurtisi and P. ovalewallikeri, respectively. We identified promising multi-copy targets for molecular detection and differentiation of P. ovalecurtisi and P. ovalewallikeri and used them to develop real-time PCR assays. The best performing P. ovalecurtisi assay performed well in singleplex and duplex formats, while the P. ovalewallikeri assay did not reliably detect low-density infections in either format. These assays have potential use for high-throughput identification of P. ovalecurtisi, or for identification of higher density P. ovalecurtisi or P. ovalewallikeri infections that are amenable to downstream next-generation sequencing.

Comparison of the Fetomaternal Outcome in Women With Preterm Premature Rupture of Membranes on Expectant Management Versus Delivery at 34 Weeks.

This study aimed to study feto-maternal outcomes in women with preterm prelabor rupture of membranes (PTPROM) on expectant management versus delivery at 34 weeks of gestation and correlate the period of latency and inflammatory markers with delivery outcomes. We have chosen this research topic as there is a paucity of specific guidelines regarding the optimal period of gestation for delivering women with PTPROM. The study correlated the feto-maternal outcomes in women with PTPROM on expectant management till 37 weeks versus delivery at 34 weeks with a period of latency and maternal inflammatory markers. This was a prospective observational study conducted on 262 women with PTPROM from 28-33+6 weeks of gestation. Women were monitored till 37 weeks with biweekly total leukocyte count and weekly C-reactive protein, urine routine microscopy, urine culture, high vaginal culturesensitivity, and ultrasound. Women were monitored expectantly till 37 weeks. However, intervention was done at any time during the feto-maternal compromise. There were 52 women who delivered <34 weeks and 210 women who delivered ≥34 weeks. Feto-maternal outcomes were documented. Group A was assigned to women who delivered before 34 weeks and Group B was assigned to women who delivered after 34 weeks. Statistical analysis was done using SPSS software.A p-value <0.05 was considered significant. Amongthe study group, 238 (90.8%) women were managed expectantly while 24(9.1%) required intervention. A latency of 3-4 weeks was observed in 131(50%) women.Chorioamnionitis developed in 7 women (4.4%) in group A and 13 women (4.9%) in group B. Neonates developed sepsis in 5.7% in group A and 5.8 % in group B and were comparable in both the groups (p=1.000). Early neonatal death (END) occurred in 10 (3.8%) amongwhich seven died because of low birth weight (LBW), two due to sepsis, and one due to respiratory distress. LBW was significantly associated with END (p<0.001) Conclusion: Expectant management beyond 34 weeks with close monitoring can improve neonatal outcomes without increasing maternal morbidity in women with PTPROM.

Bilateral Spontaneous Adrenal Hematoma: A Case Report. Diagnostic Approach and Literature Review

Spontaneous adrenal hematomas are rare and have multiple etiologies. It is characterized by clinical latency and can be mistaken for a malignant adrenal tumor. Here, we report a rare case of bilateral spontaneous adrenal hematoma in a 66-year-old patient. Preoperative diagnosis was established using computed tomography (CT). Bilateral adrenalectomy was performed, and pathological examination revealed an isolated hematoma without associated adrenal abnormalities.

OCCUPATIONAL DISEASES

Occupational diseases continue to be one of the major health problems of the able-bodied population worldwide. The reasons for this are numerous, but the main one is of course the nature of these diseases which by definition are chronic, progressive and degenerative, and the period of latency in which the disease does not have to manifest clinically can last for decades. The factors that can contribute to the development of an occupational disease, ie disease, are numerous and range from chemical, physical and biological to psychosocial risks, so there is a need to find new ways to control long-known risks, to observations of the most common workplace pathologies in the last twenty years, such as recurrent traumatic illnesses, immunodeficiency transmitted as a result of biological injuries and violence, and psychological trauma in the workplace. The aim of this paper is to evaluate the effect of noise as a function of its levels and the duration of workplace exposure on workers' health. This study was conducted with 10 workers from the metal factory "Zhelezara", Skopj which have been exposed to the noise the longest period. According to the results of the research, it can be noted that workers working in a noisy environment experience certain side effects from the noise, although they use different protective equipment for the entire duration of the working time. New knowledge in occupational health and safety practice is needed to respond to new challenges in this field.

Psoriasiform drug eruption: A case series with a review of the literature.

The present case series examined five instances of psoriasiform drug eruption diagnosed between 2014 and 2022 at the study site and 23 cases of drug eruption manifesting psoriasiform lesions which had been reported between 1986 and 2022. The causative drug, distribution of the skin eruptions, clinical latency to eruption, treatment course, and histopathological findings were investigated. The most common causative agents were calcium channel blockers (CCB) (64.5%). Of the 28 cases of psoriasiform drug eruption for which details of the eruption sites were reported, 46.4% occurred on the face, which was slightly higher than the usual distribution of psoriasis. CCB were responsible for 80.0% of the cases of facial skin rash. The mean time from the administration of the suspected drug to eruption onset was 25.0 months (range: 0.5-120 months; median: 13.0 months). In all the cases, the skin rash improved after the causative drug was discontinued. CCB were the most common causative agent, and the eruptions more commonly occurred on the face than in normal psoriasis, suggesting that it is especially important to confirm whether there is a history of CCB administration in psoriasis patients with extensive, facial skin eruptions.

Exploring the Link between Varicella-Zoster Virus, Autoimmune Diseases, and the Role of Recombinant Zoster Vaccine.

The varicella-zoster virus (VZV) is a human neurotropic herpes virus responsible for varicella and herpes zoster (HZ). Following primary infection in childhood, VZV manifests as varicella (chickenpox) and enters a period of latency within the dorsal root ganglion. A compromised cellular immune response due to aging or immunosuppression triggers viral reactivation and the development of HZ (shingles). Patients with autoimmune diseases have a higher risk of developing HZ owing to the immunodeficiency associated with the disease itself and/or the use of immunosuppressive agents. The introduction of new immunosuppressive agents with unique mechanisms has expanded the treatment options for autoimmune diseases but has also increased the risk of HZ. Specifically, Janus kinase (JAK) inhibitors and anifrolumab have raised concerns regarding HZ. Despite treatment advances, a substantial number of patients suffer from complications such as postherpetic neuralgia for prolonged periods. The adjuvanted recombinant zoster vaccine (RZV) is considered safe and effective even in immunocompromised patients. The widespread adoption of RZV may reduce the health and socioeconomic burdens of HZ patients. This review covers the link between VZV and autoimmune diseases, assesses the risk of HZ associated with immunosuppressant use, and discusses the benefits and risks of using RZV in patients with autoimmune diseases.

Abstract PR007: Delineating functional drivers of esophageal adenocarcinoma to identify synthetic lethal interactions

Abstract Application of molecular targeted therapies for esophageal adenocarcinoma (EAC) has been limited by a lack of druggable oncogenic drivers. We propose that synthetic lethal interactions may provide new opportunities for targeted therapies in EAC. We have taken an integrated multi-omics approach incorporating Perturb-Seq (CRISPR editing combined with single cell RNA sequencing) and in vivo tumorigenesis assays to perform high-throughput characterisation of &amp;gt;70 high-confidence EAC driver genes, and genome-wide CRISPR-Cas9 knockout screens in isogenic models of EAC tumorigenesis to identify disease relevant synthetic lethal genetic interactions. MS-based proteomics, reverse phase protein arrays, polysome profiling and bulk RNA-sequencing of isogenic models were utilised to interrogate the biology of bona fide EAC drivers and associated driver specific gene dependencies. The overall goals were to (i) enhance our understanding of EAC tumorigenesis, (ii) identify potential opportunities for therapeutic interventions targeting EAC drivers via synthetic lethal-like approaches, and (iii) reduce the complexity of genetic heterogeneity by categorising EAC drivers with similar phenotypic outcomes. Through our approach we have identified complex crosstalk between the tumor suppressor SMAD4 and regulation of mTOR signaling, with specific downstream effects on translational reprogramming in EAC. Mutation or loss of SMAD4 occurs in up to 20% of EAC, but not pre-malignant tissue (Barrett’s esophagus), and is sufficient to promote transformation of pre-malignant cells in our in vivo tumorigenesis model. In this model, xenotransplanted SMAD4-deficient (via CRISPR-Cas9 knockout or shRNA knockdown) Barrett’s metaplasia cells formed invasive, metastatic tumors after a period of latency. SMAD4 deficient cells had downregulated expression of 4E-BP1, which inhibits EIF4E, the cap-dependent translation initiation factor. This was accompanied by increased mTOR activity, including phosphorylation and inactivation of 4EBP1. Moreover, we found that SMAD4-deficient cells preferentially upregulate cap-dependent translation at the expense of IRES mediated translation. Furthermore, perturbation of additional negative regulators of mTOR signaling in combination with SMAD4 knockout exacerbated these effects and accelerated tumorigenesis in vivo. We have extended these findings to a model of Barrett’s esophagus patient-derived organoids (PDOs) and observed increased proliferative potential of our genetically modified PDOs. Finally, analysing gene ontologies for differentially expressed genes from Perturb-seq revealed that driver-dependent transcriptional changes can be categorized into a smaller number of functional pathways allowing us to potentially consider groups of drivers as functional units. This work advances our understanding of EAC tumorigenesis, provides new mechanistic insights into SMAD4-driven transformation as well as novel potential therapeutic avenues for SMAD4-deficient EAC. Citation Format: Julia V. Milne, Ebtihal Mustafa, Kenji Fujihara, Eric Kusnadi, Anna Trigos, Niko Thio, Maree Pechlivanis, Carlos Cabalag, Twishi Gulati, Kaylene Simpson, Cuong Duong, Luc Furic, Wayne Phillips, Nicholas Clemons. Delineating functional drivers of esophageal adenocarcinoma to identify synthetic lethal interactions [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr PR007.

The Global Impact of HIV: A Comprehensive Review

The Human Immunodeficiency Virus (HIV) has been a significant global health challenge since its discovery in the 1980s, leading to the devastating Acquired Immunodeficiency Syndrome (AIDS). Despite advancements in medical research and antiretroviral therapies, HIV/AIDS remains a pressing public health concern, particularly in resource-limited regions. This comprehensive review provides updated data and scientific insights on the global impact of HIV, shedding light on the current state of the epidemic and the challenges faced in combating it. The review highlights the resurgence of HIV cases in Eastern European countries, such as Ukraine, Estonia, and Latvia, with surprising increases in AIDS cases observed in East Asian countries. However, it is in sub-Saharan Africa that the burden of HIV remains most acute, with high prevalence rates and a significant number of affected individuals. The region requires continued attention and resources to address the complex challenges associated with HIV prevention, treatment, and care. The article delves into the classification and structure of HIV, emphasizing its belonging to the Lentivirinae subfamily, specifically HIV-1 and HIV-2. HIV-1, the predominant viral species globally, exhibits a distinct clinical latency phase, contributing to its persistence and infectivity. The high replication rate and genetic variability of HIV, driven by the error-prone reverse transcriptase enzyme, result in the emergence of diverse subtypes and strains across different regions. Furthermore, the article explores the structural components of HIV-1, including the envelope glycoproteins (gp120 and gp41), matrix protein, and various enzymes critical to the viral life cycle. Despite progress in medical research and access to antiretroviral therapies, HIV/AIDS continues to present challenges such as limited resources, drug resistance, and regional disparities.

Manual acupuncture ameliorates inflammatory pain by upregulating adenosine A3 receptor in complete Freund’s adjuvant-induced arthritis rats

BackgroundAdenosine A3 receptor (A3R) exerts analgesic, anti-inflammatory, and anti-nociceptive effects. In this study, we determined the analgesic mechanism of manual acupuncture (MA) in rats with complete Freund's adjuvant (CFA)-induced arthritis and explored whether MA ameliorates inflammation in these rats by upregulating A3R. MethodsSixty Sprague Dawley (SD) rats were randomly divided into the following groups: Control, CFA, CFA + MA, CFA + sham MA, CFA + MA + DMSO, CFA + MA + IB-MECA, and CFA + MA + Reversine groups. The arthritis rat model was induced by injecting CFA into the left ankle joints. Thereafter, the rats were subjected to MA (ST36 acupoint) for 3 days. The clinical indicators paw withdrawal latency (PWL), paw withdrawal threshold (PWT), and open field test (OFT) were used to determine the analgesic effect of MA. In addition, to explore the effect of A3R on inflammation after subjecting arthritis rats to MA, IB-MECA (A3R agonist) and Reversine (A3R antagonist) were injected into ST36 before MA. ResultsMA ameliorated the pathological symptoms of CFA-induced arthritis, including the pain indicators PWL and PWT, number of rearing, total ambulatory distance, and activity trajectory. Furthermore, after MA, the mRNA and protein expression of A3R was upregulated in CFA-induced arthritis rats. In contrast, the protein levels of TNF-α, IL-1β, Rap1, and p-p65 were downregulated after MA. Interestingly, the A3R agonist and antagonist further downregulated and upregulated inflammatory cytokine expression, respectively, after MA. Furthermore, the A3R antagonist increased the degree of ankle swelling after MA. ConclusionMA can alleviate inflammatory pain by inhibiting the NF-κB signaling pathway via upregulating A3R expression of the superficial fascia of the ST36 acupoint site in CFA-induced arthritis rats.

Building trust takes time: limits to arbitrage for blockchain-based assets

Abstract A blockchain replaces central counterparties with time-consuming consensus protocols to record the transfer of ownership. This settlement latency slows cross-exchange trading, exposing arbitrageurs to price risk. Off-chain settlement, instead, exposes arbitrageurs to costly default risk. We show with Bitcoin network and order book data that cross-exchange price differences coincide with periods of high settlement latency, asset flows chase arbitrage opportunities, and price differences across exchanges with low default risk are smaller. Blockchain-based trading thus faces a dilemma: Reliable consensus protocols require time-consuming settlement latency, leading to arbitrage limits. Circumventing such arbitrage costs is possible only by reinstalling trusted intermediation, which mitigates default risk.

A300 ADVANCED HEPATIC ECHINOCOCCOSIS: A CASE REPORT

Abstract Background Alveolar echinococcosis (AE) is a rare and potentially fatal disease caused by the parasite echinococcus multilocularis (EM). Humans are intermediate hosts who become infected through contact with definitive hosts (foxes, wolves, coyotes, dogs and cats) and ingestion of contaminated food and water. AE primarily affects the liver but has the potential for local or metastatic spread. It has a clinical latency time of 5-15 years and resembles a malignancy in appearance and growth, posing a challenge in diagnosis and management. Treatment includes benzimidazole therapy and surgical resection, however, removal of the entire parasitic mass is not always possible. Aims Present a case of hepatic AE involving the gallbladder, biliary tree, and spleen. Methods Case report. Results A 49-year-old farmer was admitted to a Saskatchewan hospital for a 2-week history of abdominal pain, jaundice, and progressive weight loss. Computed tomography (CT) of the abdomen and pelvis showed a necrotic mass in the gallbladder compromising the liver, splenic lesions and involvement of the biliary tree. The patient was given a preliminary diagnosis of metastatic cholangiocarcinoma and underwent a gallbladder biopsy which returned as echinococcus, confirmed with two liver biopsies and a positive EM nucleic acid test. He was then diagnosed with advanced hepatic AE with metastasis to the gallbladder, biliary tree, and spleen. The patient required a long-term hepatic drain and developed a hepatocutaneous fistula. While surgery is curative, his disease was too extensive for resection. He was started on Albendazole and received into our care for a liver transplant assessment 10 months later. Currently, there is limited literature on liver transplantation in advanced AE as it may not be curative. Additionally, subsequent immunosuppression may expedite residual parasite growth leading to aggressive disease recurrence. In this case, liver transplant would also require a splenectomy and excision of the hepatocutaneous fistula for complete parasite removal. Repeat CT of the abdomen and pelvis at thirteen months after the patient's initial hospitalization did not show disease progression. Given his stability on Albendazole, the added surgical complexity, and possibility of aggressive disease recurrence post liver-transplant, the multidisciplinary committee decided against liver transplant at this time. He continues to do well on Albendazole 15 months after initial presentation. Conclusions The reported mortality rate of AE is ampersand:003E 90% within 10-15 years of diagnosis if untreated or inadequately treated. This case highlights the complexities in management of advanced hepatic AE and the importance of early diagnosis and treatment with radical surgery. Although not curative, benzimidazole therapy is effective in slowing disease progression in unresectable cases. Further studies are needed to assess the role of liver transplantation in advanced hepatic AE. Funding Agencies None

Characteristics and immune checkpoint status of radioiodine-refractory recurrent papillary thyroid carcinomas from Ukrainian Chornobyl Tissue Bank donors.

The radioiodine-refractory (RAI-R) recurrent papillary thyroid carcinomas (PTCs) are more frequent in elderly patients and have an unfavorable prognosis. Data on the prevalence and characteristics of RAI-R recurrent PTCs in patients of young and middle age with or without a history of radiation exposure in childhood are poorly described. The aim of the current study was: i) to determine the frequency of RAI-R recurrent PTCs among donors of the Chornobyl Tissue Bank (CTB) and analyze the clinicopathological features of primary tumors (PTs), primary metastases (PMTSs), recurrent metastases (RMTSs) and risk factors for RMTS, and ii) to determine the immune checkpoint status (ICS) of the RAI-R recurrent PTCs and to assess the factors associated with ICS positivity. Sixty RAI-R recurrent PTCs (46 exposed to radiation and 14 non-exposed, 2.5% of all cases registered with the CTB) from the Ukrainian patients aged up to 48 years were identified. The clinicopathological characteristics of the PTs moderately to weakly resembled those of the PMTS and RMTS from the same patients while the metastatic tissues were highly similar. The multivariate model of RMTS included the dominant solid-trabecular growth pattern of the PT, cystic changes, N1b metastases, and the probability of a causation (POC) of PTC by radiation as risk factors. Among these factors, the lateral PMTS (N1b) had the strongest effect. The longer period of latency (a POC component) was the second statistically significant characteristic. ICS percent agreement between the PT and RAI-R RMTS was 91.5%; 23.7% of PTs and 28.8% of RMTSs had positive ICS (positive PD-L1 tumor epithelial cells (TECs) and positive PD-L1/PD1 tumor-associated immune cells). ICS positivity of PTs was associated with pronounced oncocytic changes and high density of the p16INK4A-positive TECs in the invasive areas of PTs. In RMTSs, ICS positivity was associated with pronounced oncocytic changes and Ki-67 labeling index ≥ 4.5% of PTs, and the dominant solid-trabecular growth pattern, Ki-67 labeling index ≥ 7.6% and p16INK4A-positivity of RMTS. The findings are of clinical relevance and may be useful for developing individual treatment approaches for patients with RAI-R recurrent PTCs possibly involving immunotherapy.

Abstract A176: Loss of SMAD4 unleashes mTOR and increases dependency on cap-dependent translation in esophageal tumorigenesis

Abstract Application of molecular targeted therapies for esophageal adenocarcinoma (EAC) has been limited by a lack of druggable oncogenic drivers. We propose that synthetic lethal interactions may provide new opportunities for targeted therapies in EAC. We have taken an integrated multi-omics approach incorporating Perturb-Seq (CRISPR editing combined with single cell RNA sequencing) and in vivo tumorigenesis assays to perform high-throughput characterisation of &amp;gt;70 high-confidence EAC driver genes, and genome-wide CRISPR-Cas9 knockout screens in isogenic models of EAC tumorigenesis to identify disease relevant synthetic lethal genetic interactions. MS-based proteomics, reverse phase protein arrays, polysome profiling and bulk RNA-sequencing of isogenic models were utilised to interrogate the biology of bona fide EAC drivers and associated driver specific gene dependencies. The overall goals were to (i) enhance our understanding of EAC tumorigenesis, (ii) identify potential opportunities for therapeutic interventions targeting EAC drivers via synthetic lethal-like approaches, and (iii) reduce the complexity of genetic heterogeneity by categorising EAC drivers with similar phenotypic outcomes. Through our approach we have identified complex crosstalk between the tumor suppressor SMAD4 and regulation of mTOR signaling, with specific downstream effects on translational reprogramming in EAC. Mutation or loss of SMAD4 occurs in up to 20% of EAC, but not pre-malignant tissue (Barrett’s esophagus), and is sufficient to promote transformation of pre-malignant cells in our in vivo tumorigenesis model. In this model, xenotransplanted SMAD4-deficient (via CRISPR-Cas9 knockout or shRNA knockdown) Barrett’s metaplasia cells formed invasive, metastatic tumors after a period of latency. SMAD4 deficient cells had downregulated expression of 4E-BP1, which inhibits EIF4E, the cap-dependent translation initiation factor. This was accompanied by increased mTOR activity, including phosphorylation and inactivation of 4EBP1. Moreover, we found that SMAD4-deficient cells preferentially upregulate cap-dependent translation and become addicted to translation of oncogenic mRNAs. Furthermore, perturbation of additional negative regulators of mTOR signaling in combination with SMAD4 knockout exacerbated these effects and accelerated tumorigenesis in vivo. We have extended these findings to a model of Barrett’s esophagus patient-derived organoids (PDOs) and observed increased proliferative potential of our genetically modified PDOs. Finally, analysing gene ontologies for differentially expressed genes from Perturb-seq revealed that driver-dependent transcriptional changes can be categorized into a smaller number of functional pathways allowing us to potentially consider groups of drivers as functional units. This work advances our understanding of EAC tumorigenesis, provides new mechanistic insights into SMAD4-driven transformation as well as novel potential therapeutic avenues for SMAD4-deficient EAC. Citation Format: Julia V Milne, Ebtihal Mustafa, Kenji Fujihara, Eric Kusnadi, Niko Thio, Maree Pechlivanis, Carlos Cabalag, Twishi Gulati, Kaylene Simpson, Cuong Duong, Luc Furic, Wayne Phillips, Nicholas J Clemons. Loss of SMAD4 unleashes mTOR and increases dependency on cap-dependent translation in esophageal tumorigenesis [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A176.

The Effects of Radial Extra Corporeal Shock Wave and Low-power Laser Therapies on Clinical and Electrophysiological Parameters in Moderate Carpal Tunnel Syndrome: A Blinded Randomized Control Trial

Objectives: Carpal tunnel syndrome (CTS) is a common peripheral entrapment neuropathy with squeezing of the median nerve and the patient is unable to function properly. There are different physiotherapy interventions for the management of these patients and recently, shock wave therapy and low-power laser (LPL) have been widely used, but there is no strong evidence comparing the effect of shock wave therapy and LLLT. Therefore, this trial was designed to compare the effect of extracorporeal shock wave therapy (ESWT), LPL, and routine interventions on clinical outcomes and electrophysiological parameters in patients with moderate CTS. Methods: Fifty-four patients were randomly assigned to the control (routine interventions), ESWT, and LPL therapy groups. All participants received transcutaneous electrical nerve stimulation (TENS) therapeutic ultrasound, hot pack, mobilization, and stretching for ten sessions over two weeks. Additionally, the ESWT group received radial ESWT in four sessions, and the LPL therapy group received laser in ten sessions. The primary outcomes were pain (assessed by the visual analog scale), function (assessed using the Boston questionnaire (BQ)), hand grip, and finger pinch strength. Secondary outcomes were electrophysiological parameters (distal motor and sensory latency and nerve conduction velocity (NCV) of the median nerve. Results: Time group interactions were significant for pain, the symptom severity subscale of BQ, finger pinch, and hand grip strength (p&lt;0.001). Significant improvements were seen in clinical and sensory latency and motor NCV of the median nerve (p&lt;0.05). The ESWT group experienced significant improvements with a large effect size in pain, function, and finger pinch strength compared to the control group (p&lt;0.01). Additionally, the LPL therapy group showed significant changes in the function and finger pinch and hand grip strength compared to the control group. There were no significant differences between the LPL therapy and ESWT groups except for pain in favor of the ESWT group. No significant differences were found among the three groups in electrophysiological parameters (p&gt;0.05). Discussion: Although laser therapy increased the efficacy of routine interventions, it seems adding ESWT to the routine treatment may be superior for the management of moderate CTS patients.

Primary Hydatid Cyst of the Rib-Case Report

Hydatid disease is an endemic zoonosis in rural countries, particularly in Algeria. It affects all organ but mainly the liver and lungs. The rib is exceptional localization. Its diagnosis is often late due to the lack of specificity and clinical latency that characterize this disease. The treatment is essentially surgical and is based on wide excision of the affected tissues. We report the case of a patient with primary rib hydatidosis treated surgically.

Acquired Immune Deficiency Syndrome correlation with SARS-CoV-2 N genotypes

BackgroundEpigenetics and clinical observations referring to Betacoronavirus lead to the conjecture that Sarbecovirus may have the ability to infect lymphocytes using a different way than the spike protein. In addition to inducing the death of lymphocytes, thus drastically reducing their population and causing a serious immune deficiency, allows it to remain hidden for long periods of latency using them as a viral reservoir in what is named Long-Covid Disease. Exploring possibilities, the hypothesis is focused on that N protein may be the key of infecting lymphocytes. MethodThe present article exhibits a computational assay for the latest complete sequences reported to GISAID, correlating N genotypes with an enhancement in the affinity of the complex that causes immune deficiency in order to determine a good docking with the N protein and some receptors in lymphocytes. ResultsA novel high-interaction coupling of N-RBD and CD147 is presented as the main way of infecting lymphocytes, allowing to define those genotypes involved in their affinity enhancement. ConclusionThe hypothesis is consistent with the mutagenic deriving observed on the in-silico assay, which reveals that genotypes N/120 and N/152 are determinant to reduce the Immune Response of the host infecting lymphocytes, allowing the virus persists indefinitely and causing an Acquire Immune Deficiency Syndrome.

The Spectrum of Neurological Manifestations of Varicella-Zoster Virus Reactivation.

Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles). The focus of this review is on the wide spectrum of the possible neurological manifestations of VZV reactivation. While the most frequent reactivation syndrome is herpes zoster, this may be followed by the serious and painful post-herpetic neuralgia (PHN) and by many other neurological conditions. Prominent among these conditions is a VZV vasculopathy, but the role of VZV in causing giant cell arteritis (GCA) is currently controversial. VZV reactivation can also cause segmental motor weakness, myelitis, cranial nerve syndromes, Guillain-Barre syndrome, meningoencephalitis, and zoster sine herpete, where a neurological syndrome occurs in the absence of the zoster rash. The field is complicated by the relatively few cases of neurological complications described and by the issue of causation when a neurological condition is not manifest at the same time as the zoster rash.

The mechanisms and diagnostic potential of lncRNAs, miRNAs, and their related signaling pathways in cervical cancer.

Cervical cancer (CC), the fourth most prevalent type of cancer among women worldwide, is associated with high rates of morbidity and mortality. Due to the long period of latency in CC, most patients are already in the middle to late stages when initially diagnosed, which greatly reduces the clinical cure rate and quality of survival, thus resulting in poor outcomes. In recent years, with continuous exploration in the fields of bioinformatics and molecules, it has been found that ncRNAs, including miRNAs and lncRNAs, without the ability to translate proteins are capable of activating or inhibiting certain signaling pathways by targeting and modulating the level of expression of proteins involved in these signaling pathways. ncRNAs play important roles in assisting with diagnosis, drug administration, and prediction of prognosis during CC progression. As an entry point, the mechanisms of interaction between miRNAs, lncRNAs, and signaling pathways have long been a focus in basic research relating to CC, and numerous experimental studies have confirmed the close relationship of miRNAs, lncRNAs, and signaling pathways with CC development. Against this background, we summarize the latest advances in the involvement of lncRNA- and miRNA-related signaling pathways in the development of CC to provide guidance for CC treatment.

Study on clinical characteristics of event-related potential P300 in elderly schizophrenics and associated risk factors.

To investigate the clinical characteristics of event-related potential P300 in elderly schizophrenics with different levels of violence and the risk factors of severe violence. A total of 138 elderly schizophrenic patients from January 2020 to December 2021 in the First Hospital of Hebei Medical University were enrolled in this retrospective analysis. Based on the violence risk assessment, 61, 102, and 145 patients were divided into high-risk, medium-risk, and low-risk groups, respectively. Clinical characteristics, P300 latency, and P300 amplitude were compared among the three groups followed by a logistic regression analysis of elderly schizophrenics with severe violence. The latency of P300 in the high-risk group was higher than that in the low-risk group (p<.05). The P300 amplitude of patients in the high-risk group was significantly lower than that in the low-risk group (p<.05). Univariate logistic regression analysis showed that previous history of violence, delusion of persecution, P300 latency, and amplitude were independent influencing factors of severe violence in elderly schizophrenics (odds ratio [OR]: 0.022, 95% confidence interval [CI]: 0.007-0.067, p<.001; OR: 0.118, 95% CI: 0.043-1.763, p=.037; OR: 1.289, 95% CI: 1.142-1.673, p<.001; and OR: 0.049, 95% CI: 0.021-0.067, p<0.001, respectively). After adjusting gender, age, and other confounding factors, multivariate logistic regression analysis showed that delusion of persecution, P300 latency, and P300 amplitude were associated with severe violence in elderly schizophrenics (OR: 2.211, 95% CI: 0.061-4.067, p<.001; OR: 2.006, 95% CI: 1.421-2.721, p=.017; and OR: 0.067, 95% CI: 0.037-0.276; p<.001; respectively). The latency and amplitude of P300 can be used as effective neuroelectrophysiological indicators to evaluate the violence level of elderly schizophrenics. Delusion of persecution, P300 latency, and P300 amplitude were independent influencing factors of severe violence in elderly schizophrenics.

Anatomical-Clinical Aspects of the Retrocaval Ureter: Report of 4 Cases and Review of the Literature

<i>Introduction:</i> Retrocaval ureter (RCU) is a birth defect, characterized by a spiral path of the ureter around the inferior vena cava. It is an abnormal in the development of the inferior vena cava, which can lead to ureteral obstruction. The aim of this study was to report 4 cases of RCU with a literature review. <i>Patients and method: </i>This was a retrospective, descriptive study in two department of urology including patients followed up and undergone a surgery for a RCU, from January 2016 to December 2021 in two tertiary hospitals of Dakar. We used radiological classification to describe the anatomical and clinical features.<i> Results: </i>Four adult patients suffering from RCU were diagnosed and treated over a 6-year period of time. Their mean age was 39 years (36 and 44 years). There were as many men as women. Low back pain was the most common sign. The Uro-CT scan showed a type I of RCU in 3 patients. For all of them, we performed an open surgical procedure to unhook the ureter followed by an uretero-ureteral anastomosis on a JJ stend. The portion of the ureter in retro cave atresic position was resected. The postoperative follow-up was simple.<i> Conclusion: </i>Retrocaval ureter is a very rare birth defect for which the right incidence is not known because of the clinical latency. Although classical surgery leads to positive outcomes, the minimally invasive approach is very promising.