High Post-Infection Protection after COVID-19 among Healthcare Workers: A Population-Level Observational Study.

Background: Even though a few years have passed since the coronavirus disease 2019 (COVID-19) outbreak, information regarding certain aspects of the disease, such as post-infection immunity, is still quite limited. This study aimed to evaluate post-infection protection and COVID-19 features among healthcare workers (HCWs), during three successive surges, as well as the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection, reactivation, re-positivity, and severity. Methods: This cross-sectional population-level observational study was conducted from 20 April 2020 to 18 February 2021. The study population included all HCWs in public or private hospitals in Fars Province, Southern Iran. The infection rate was computed as the number of individuals with positive polymerase chain reaction (PCR) tests divided by the total number of person-days at risk. The re-infection was evaluated after 90 days. Results: A total of 30,546 PCR tests were performed among HCWs, of which 13,749 (61.94% of total HCWs) were positive. Considering the applied 90-day threshold, there were 44 (31.2%) cases of reactivation and relapse, and 97 (68.8% of infected and 1.81% of total HCWs) cases of reinfection among 141 (2.64%) diagnosed cases who experienced a second episode of COVID-19. There was no significant difference in symptoms (P=0.65) or the necessity for ICU admission (P=0.25). The estimated protection against repeated infection after a previous SARS-CoV-2 infection was 94.8% (95% CI=93.6-95.7). Conclusion: SARS-CoV-2 re-positivity, relapse, and reinfection were rare in the HCW population. After the first episode of infection, an estimated 94.8% protection against recurring infections was achieved. A preprint version of this manuscript is available at DOI:10.21203/rs.3.rs-772662/v1 (https://www.researchsquare.com/article/rs-772662/v1).

Seizure first aid for people with epilepsy: opinions and knowledge of caregivers and healthcare professionals.

OBJECTIVE: We investigated the opinions and knowledge of the caregivers of people with epilepsy (PWE) and the related healthcare professionals (i.e., nurses and physicians) in Iran about first aid measures for helping a person experiencing a seizure. METHODS: In this exploratory and descriptive study, we surveyed the caregivers of all PWE admitted to the epilepsy monitoring unit at Namazi Hospital, Shiraz, Iran, in May 2022. We also surveyed all the nurses at this hospital. A similar survey was distributed in the WhatsApp groups of the neurology, pediatrics, internal medicine, family physician, psychiatry, and neurosurgery physicians working at places affiliated with Shiraz University of Medical Sciences, Shiraz, Iran. RESULTS: In total, 583 nurses, 70 physicians, and 133 caregivers participated in this study. On most questions, more caregivers provided inappropriate responses than nurses and physicians (e.g., not timing the seizure; not loosening the clothes around the neck; not rolling the patient onto the side if unconscious). On two questions, more caregivers provided appropriate responses than nurses and physicians (i.e., not putting something into the mouth; not always calling for emergency medical services). CONCLUSION: While some actions may help prevent or reduce the chance of harmful consequences of epileptic seizures, many caregivers of PWE and healthcare professionals do not apply appropriate measures to help a patient experiencing a seizure. The scientific community should develop standardized seizure first aid training programs for the general public and healthcare professionals alike.

Preclinical study of formulated recombinant nucleocapsid protein, the receptor binding domain of the spike protein, and truncated spike (S1) protein as vaccine candidates against COVID-19 in animal models.

BACKGROUND: In this pre-clinical study, we designed a candidate vaccine based on severe acute respiratory syndrome-related -coronavirus 2 (SARS-CoV-2) antigens and evaluated its safety and immunogenicity. METHODS: SARS-CoV-2 recombinant protein antigens, including truncated spike protein (SS1, lacking the N-terminal domain of S1), receptor-binding domain (RBD), and nucleoprotein (N) were used. Immunization program was performed via injection of RBD, SS1 +RBD, and SS1 +N along with different adjuvants, Alum, AS03, and Montanide at doses of 0, 40, 80, and 120 µg at three-time points in mice, rabbits, and primates. The humoral and cellular immunity were analyzed by ELISA, VNT, splenocyte cytokine assay, and flow cytometry. RESULTS: The candidate vaccine produced strong IgG antibody titers at doses of 80 and 120 µg on days 35 and 42. Even though AS03 and Montanide produced high-titer antibodies compared to Alum adjuvant, these sera did not neutralize the virus. Strong virus neutralization was recorded during immunization with SS1 +RBD and RBD with Alum. AS03 and Montanide showed a strong humoral and cellular immunity; however, Alum showed mild to moderate cellular responses. Ultimately, no cytotoxicity and pathologic change were observed. CONCLUSION: These findings strongly suggest that RBD with Alum adjuvant is highly immunogenic as a potential vaccine.

Entamoeba histolytica and Probable Effect on Production Microsatellite Instability in Colorectal Cancer.

The mortality rate of Entamoeba histolytica is still high and approximately 100,000 per year. Environmental factors and different pathogens can cause microsatellite instability (MSI) positive, which may be one reason for colorectal cancer. MSI status can play an essential role in treatment. Moreover, E. histolytica might be one of the pathogens which raise the incidence of colorectal cancer. Therefore, the probable relationship of E. histolytica with MSI production was evaluated. Four hundred samples of colorectal biopsies based on pathological reports were divided into four groups: colitis, polyps, hyperplasia or dysplasia, and adenocarcinoma. The prevalence of E. histolytica was examined with PCR and immunohistochemical staining (IHC) for the light chain lectin HK-9. The adenocarcinoma formalin-fixed paraffin-embedded colorectal tumours sections were tested for MSI genes. We detected E. histolytica in 6% and 4% of colitis samples by PCR and IHC technique, respectively. However, it did not identify in polyp and hyperplasia samples. The MSI test was examined in the colorectal cancer group, which became positive in 19%. Entamoeba histolytica was detected in 26.3% (5/19) of MSI-positive and 2.5% (2/81) of MSI-negative cases by IHC technique however was not identified by PCR assay in this group. It is concluded PCR and IHC assay is recommended as complementary tests in colitis biopsies. Simultaneous PCR and IHC negative results could confirm the non-existence of the parasite with more confidence. Consequently, E. histolytica might be one of the biotic  factors which raise the incidence of colorectal cancer because of the coincidence of the IHC positive results in MSI-positive adenocarcinoma.

Estradiol modulated differentiation and dynamic growth of CD90+ spermatogonial stem cells toward Sertoli-like cells.

Mouse CD90+ SSCs were enriched using the MACS technique and incubated with different doses of estradiol, ranging from 0.01 ng/mL to 500 µg/mL, for 7 days. The viability of SSCs was determined using an MTT assay. The combined effects of estradiol plus Sertoli cell differentiation medium on the orientation of SSCs toward Sertoli-like cells were also assessed. Using immunofluorescence imaging, we monitored protein levels of Oct3/4 after being exposed to estradiol. In addition, protein levels of testosterone, TF, and ABP were measured using ELISA. The expression of Sertoli cell-specific genes such as SOX9, GATA4, FSHR, TF, and ESR-1 and -2 was monitored using real-time PCR assay, and the effects of 14-day injection of estradiol on sperm parameters and Oct3/4 positive progenitor cells in a model of mouse were determined. Data showed that estradiol increased the viability of mouse SSCs in a dose-dependent manner compared to the control (p < 0.05). Along with these changes, cells displayed morphological changes and reduced Oct3/4 transcription factor levels compared to the control SSCs. 7-day incubation of SSCs with estradiol led to the up-regulation of SOX9, GATA4, FSHR, TF, and ESR-1 and -2, and levels of testosterone, TF, and ABP were increased compared to the control group (p < 0.05). The in-vivo examination noted that estradiol reduced sperm parameters coincided with morphological abnormalities (p < 0.05). Histological examination revealed pathological changes in seminiferous tubules and reduction of testicular Oct3/4+ progenitor cells. In conclusion, estradiol treatment probably can induce Sertoli cell differentiation of SSCs while exogenous administration leads to testicular progenitor cell depletion and infertility in long term.

Acute invasive fungal rhinosinusitis: Molecular identification and update in management of frozen section biopsy.

The clinical diagnosis of Acute Invasive Fungal Rhinosinusitis (AIFRS) is technically difficult because it presents with non-exclusive and nonspecific clinical symptoms. Laboratory confirmation (usually via histopathologic techniques such as formalin-fixed paraffin-embedded (FFPE)) is necessary but it is time-consuming, despite the urgent need for timely diagnosis of AIFRS for effective management. This study aimed to investigate the sensitivity and specificity of the GMS frozen-section biopsy in the diagnosis of AIFRS and compare the same with that of different tissue staining methods to provide valid decision-grounds that may guide clinicians in prompt diagnosis of acute fungal invasive rhinosinusitis. A cross-sectional study was conducted in the Medical Mycology Laboratory, Faculty of Medicine, Iran University of Medical Sciences between 2018 and 2020 on 200 patients with suspected AIFRS referred to Baqiyatallah and Imam Khomeini Hospital, Tehran. All patients were subjected to diagnostic nasal endoscopy and computed tomography (CT) scan of paranasal sinuses. Magnetic resonance imaging (MRI) was done in cases of suspected intracranial extension. After screening by routine mycological examination, the diagnosis was confirmed using complementary molecular methods. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the frozen-section biopsy were also compared with FFPE. Of the 200 suspect patients, 47 cases (23.5%) met the criteria for AIFRS. Species of the genus Aspergillus were the predominant 27 (57.4%) followed by Mucorales species 10 (21.3%), and Fusarium spp 3 (6.4%). Also, 3 cases (6.4%) of co-infection due to Aspergillus/Rhizopus were reported. The accuracy, sensitivity, specificity, PPV, and NPV of frozen section assessments were 99.5%, 97.9%, 100%, 100% and 99.3%, respectively. For GMS frozen-section alone, sensitivity, specificity, NPV, and PPV was 100%. Overall, the calculated accuracy of FFPE was 98.5%, sensitivity was 94%, specificity was 100%, PPV was 100%, and NPV was 98.1%. Examination of the frozen-section biopsy is a highly predictive tool for a rapid and effective diagnosis of patients with suspected AIFRS. We observed that GMS frozen-section is a fast and reliable exam to confirm the diagnosis of fungal invasion, with good accuracy, sensitivity, and specificity compared to the gold-standard FFPE biopsy.

Molecular Examination of Trichomonas vaginalis Infection and Risk of Prostate Cancer in the Biopsy of Patients with Different Prostate Lesions.

BACKGROUND: Trichomoniasis is a sexually transmitted infectious disease caused by a flagellated protozoa, Trichomonas vaginalis (T.vaginalis) and is often asymptomatic in men. Benign prostatic hyperplasia (BPH) and prostate cancer (PCA) are the most common urological diseases in the elderly. Scientists have proposed various factors which trigger prostate cancer, including sexually transmitted diseases. Thus, this study aimed to evaluate the potential role of T. vaginalis as a risk factor for various prostate lesions such as hyperplasia and prostate cancer. METHODS: A total of 250 paraffin-embedded of different prostate lesion biopsies were analyzed by Polymerase Chain Reaction (PCR) using the beta-tubulin gene for identifying T. vaginalis. RESULT: All 250 pathologic specimens were negative for this parasite by using PCR technique. CONCLUSION: It seems that T. vaginalis may have not had a causative role for different prostate lesions and it seems proposed PCR technique is an insufficient method to find the parasite in paraffin-embedded tissues. Therefore, other diagnostic techniques to identify the parasite in biopsy samples are suggested.

A Challenging Diagnosis of Two Ruptured and Intact Pulmonary Echinococcal Cysts in a 54-Year-Old Woman: A Case Report.

PURPOSE: Echinococcosis is one of the most important parasitic zoonotic diseases around the world. Echinococcus granulosus is the most widespread species of the genus Echinococcus that can develop cysts in different parts of the body. We tried to present a case of pulmonary cystic echinococcosis. METHODS: Here, we report a rare case of two ruptured and intact cysts in a 54-year-old woman with weakness, lethargy, body pain, stomachache, dizziness, and vision problems. RESULTS: According to the patient's manifestations and imaging findings, besides the COVID-19 pandemic, she was suspected of having COVID-19 and tuberculosis. However, when the aspirated sample was stained, hooklets of E. granulosus were observed. Surgical removal and chemotherapy were used for treatment. CONCLUSION: Treatment of pulmonary cystic echinococcosis is based on surgery, but, along with it, the chemotherapy makes a better prognosis.

COVID-19 infection among healthcare workers: a cross-sectional study in southwest Iran.

OBJECTIVE: With the novel coronavirus pandemic, the impact on the healthcare system and workers cannot be overlooked. However, studies on the infection status of medical personnel are still lacking. It is imperative to ensure the safety of health-care workers (HCWs) not only to safeguard continuous patient care but also to ensure they do not transmit the virus, therefore evaluation of infection rates in these groups are indicated. METHODS: Demographic and clinical data regarding infected cases among HCWs of Fars, Iran with positive SARS-CoV-2 PCR tests were obtained from 10th March to 17th May 2020. RESULTS: Our data demonstrated a rate of 5.62% (273 out of 4854 cases) infection among HCW, with a mean age of 35 years and a dominance of female cases (146 cases: 53.5%). The majority of infected cases were among nurses (51.3%), while the most case infection rate (CIR) was among physicians (27 positive cases out of 842 performed test (3.2%)). Also, the highest rate of infection was in the emergency rooms (30.6%). Also, 35.5% of the patients were asymptomatic and the most frequent clinical features among symptomatic patients were myalgia (46%) and cough (45.5%). Although 5.5% were admitted to hospitals, there were no reports of ICU admission. Furthermore, 10.3% of the cases reported transmitting the infection to family and friends. Regarding safety precautions, 1.6% didn't wear masks and 18.7% didn't use gloves in work environments. CONCLUSION: HCWs are among the highest groups at risk of infection during the COVID-19 pandemic; therefore, evaluating infection rates and associated features is necessary to improve and adjust protective measures of these vulnerable, yet highly essential group.

Melatonin and prolonged physical activity attenuated the detrimental effects of diabetic condition on murine cardiac tissue.

In this study, the combined effects of four-week swimming training and melatonin were examined on the oxidative response, inflammation, apoptosis, and angiogenesis capacity of cardiac tissue in the mouse model of diabetes. The mice were randomly allocated into five groups (n = 10 per group) as follows: Control; Diabetic group; Diabetic + Melatonin group; Diabetic + Exercise group; and Diabetic + Exercise + Melatonin group. 50 mg/kg streptozotocin was intraperitoneally administrated. In melatonin-treated groups, melatonin was injected intraperitoneally at 3 mg/kg body weight for four weeks and twice weekly. Swimming exercises were performed for four weeks. We measured cardiac superoxide dismutase, glutathione peroxidase enzymes, malondialdehyde, and total antioxidant capacity. The expression of tumor necrosis factor-α, Caspase­3, Sirtuin1, and Connexin-43 was measured using real-time PCR analysis. The vascular density was analyzed by immunohistochemistry using CD31 and α-smooth muscle actin antibodies. The combination of melatonin and exercise elevated cardiac superoxide dismutase, glutathione peroxidase coincided with the reduction of malondialdehyde and increase of total antioxidant capacity as compared to the diabetic mice (p < 0.05). In Diabetic + Exercise + Melatonin mice, tumor necrosis factor-α, Caspase­3 was significantly down-regulated compared to the Diabetic group (p < 0.05). Melatonin and exercise suppressed the expression of Connexin-43 and Sirtuin1 in diabetic mice in comparison with the control mice (p < 0.05). H & E staining showed necrosis and focal hyperemia reduction in the Diabetic + Exercise + Melatonin group compared to the Diabetic group. Data showed a decrease of CD31+ and α-smooth muscle actin+ vessels in the Diabetic group as compared to the normal samples (p < 0.05). The number of CD31+ vessels, but not α-smooth muscle actin+ type, increased in the Diabetic + Exercise + Melatonin group compared to the Diabetic mice. These data demonstrated that exercise along with melatonin administration could diminish the detrimental effects of diabetes on cardiac tissue via using different mechanisms.

Distribution of invasive fungal infections: Molecular epidemiology, etiology, clinical conditions, diagnosis and risk factors: A 3-year experience with 490 patients under intensive care.

Recently, the prevalence of invasive fungal infections (IFIs) is rising. The global mortality rate of IFIs is 10-49%. This study aimed to determine the prevalence, the causative agents, and the risk factors associated with the invasive fungal infections in a tertiary health center to provide valid decision-grounds for healthcare professionals to effectively prevent, control, and treat fungal infections. The current study was conducted on 1477 patients suspected to have systemic fungal infections from different units of the hospital. After screening using routine mycological examination, the patients were confirmed with complementary mycological and molecular methods. Patients were included based on the confirmed diagnosis of IFI and excluded based on lack of a microbiologically and histologically proven diagnosis of IFI. Of the 1477 patients recruited in this study, confirmed cases of fungal infection were 490 (169 proven; 321 cases probable). Among the fungi recovered, Candida species had the highest frequency 337 (68.8%) followed by Aspergillus species 108 (22.1%), Zygomycetes species 21 (4.3%), non-Candida yeast 9 (1.8%). Others were black fungi 5 (1%), mycetoma agents 5 (1%), Fusarium 4 (0.8%), and Trichoderma (0.2%). Hematologic malignancies and diabetes mellitus were the most common underlying diseases among IFI-confirmed patients. This study observed an increased frequency of invasive candidiasis with non-albicans Candida and other invasive saprophytic fungal infections. The increased rate of invasive candidiasis with non-albicans agents highlights a new perspective in the epidemiology and treatment of invasive fungal infections.

Characteristics of deceased patients with CoVID-19 after the first peak of the epidemic in Fars province, Iran.

Emergence of a new coronavirus causes a serious concern whether this can be stopped at all. The ongoing coronavirus disease created a substantial variation in the fatality rate over the world. The current report brought an explore about the epidemiological characteristics of deceased patients and the fatality rate after the first peak in Fars province which is the fourth most populous and large province in Iran. Of the 3702 confirmed cases with coVID-19, 87 patients passed away and so the fatality rate estimated 2.35. Also, it was derived that male sex, old age and underlying diseases especially diabetes were common characteristics of these victims.

Vesical schistosomiasis and squamous cell carcinoma associated with schistosoma haematobium: A re-emerging neglected tropical disease in Tehran, Iran.

Hematobium species of this parasite tends to bladder and mesenteric arteries and it causes lesions in the bladder wall, urethra, and renal tubes. A 25-year-old man living in Tehran (a non-endemic and very rare area for schistosoma) suffers from symptoms such as hematuria with suprapubic pain, dysuria, fever, nausea and vomiting. Urine analysis showed a lot of red blood cells, after using cystoscopy of the area and receiving a bladder biopsy, a definitive diagnosis of schistosomiasis was made and after determining the extent of damage to the urinary tract, appropriate treatment with surgery and praziquantel (40 mg/kg) were prescribed.

Modulatory effect of photobiomodulation on stem cell epigenetic memory: a highlight on differentiation capacity.

Differentiation potential of stem cells into various lineages makes these cells as promising sources to treat multiple diseases. In this regard, the use of different strategies and protocols to increase differentiation capacity is highly demanded. Low-level laser therapy, a relatively noninvasive technique, has the capacity to accelerate the healing of numerous injuries and a portion of restorative capacity could be correlated with the stem cell activation and differentiation. Several mechanisms have been diagnosed to participate in orientation of stem cells to functional mature cells. Among them, the status of DNA methylation orchestrates the maintenance of tissue-specific gene expression during the differentiation procedure. DNA methylation is a momentous event in embryogenesis and functional maturation. This review article highlighted the potency of laser irradiation (low-level intensities) in the differentiation of stem cells by modulation of methylation. The analysis of these modalities could help us to understand the underlying mechanisms participating in the therapeutic effects of photobiomodulation.

Mass capture and anesthesia of Australian bridled nailtail wallabies (Onychogalea fraenata) with the use of medetomidine and ketamine.

We anesthetized 301 bridled nailtail wallabies (Onychogalea fraenata), captured within Scotia Sanctuary, New South Wales, Australia over four nights in October 2009 to perform health assessments before their release into a predator-proof exclosure. We tested two anesthetic dose-rate combinations, protocol 1 (0.08 mg/kg medetomidine-4.5 mg/kg ketamine), and protocol 2 (0.1 mg/kg medetomidine-5 mg/kg ketamine), each given intramuscularly. Median time from injection to recumbency for protocol 1 was 10 min (1-27 min) and for protocol 2 was 12 min (2-28) (P=0.12). Five animals died during the induction with protocol 2; none died with protocol 1 (P=0.06). Physiologic parameters were recorded during recumbency, with no significant abnormalities with protocol 1. Protocol 1 was an effective, efficient regime to anesthetize large numbers of bridled nailtail wallabies under field conditions.