X-Linked Familial Hypophosphatemia: A Case Report of 27-Year Old Male and Review of Literature.

X-linked hypophosphatemia (XLH) associated with short stature during childhood are mostly referred to the hospital and diagnosed as vitamin D deficiency rickets and received vitamin D before adulthood. A case is presented with clinical features of hypophosphatemia from childhood who did not seek medical care for diagnosis and treatment, nor did his mother or two brothers, who have short statures, bone pain, and fractures. The patient was assessed for sociodemographic, hematological, and biochemical parameters together with a genetic assessment. A DEXA scan and X-ray were done to determine the abnormalities and deformities of joints and bones despite clinical examination by an expert physician. All imaging, laboratory parameters, and the genetic study confirmed the diagnosis of XLH. A detailed follow-up of his condition was performed after the use of phosphate tablets and other treatments. X-linked hypophosphatemia needs a good assessment, care, and follow up through a complementary medical team including several specialties. Phosphate tablets in adulthood significantly affects clinical and physical improvement and prevention of further skeletal abnormality and burden on daily activity. The patients should be maintained with an adequate dose of phosphate for better patient compliance. More awareness is needed in society and for health professionals when conducting medical checkups during the presence of stress fractures, frequent dental and gum problems, rickets, short stature, or abnormality in the skeleton or walking to think of secondary causes such as hypophosphatemia. Further investigations including a visit to a specialist is imperative to check for the primary cause of these disturbances.

Long-term toxicity of fluoroquinolones: a comprehensive review.

Fluoroquinolones (FQs) are highly potent bactericidal antibiotics with broad-spectrum activity against Gram-negative/positive bacteria. The Food and Drug Administration (FDA) anticipated the presence of a long-lasting incapacity of Fluoroquinolone Associated Toxicity (FQAT), which is not officially documented yet. This review aimed to précis the existing information on FQA long-term toxicity, such as cardiotoxicity, aortic aneurysm, tendon rupture, nephrotoxicity, hepatotoxicity, peripheral neuropathy, vagus nervous dysfunction, reactive oxygen species (ROS), phototoxicity, glucose hemostasis, and central nervous system (CNS) toxicity. We are focused on the CNS toxicity of FQs, either due to the direct action of the FQs on CNS receptors or by other drug co-administration, including nonsteroidal anti-inflammatory disease (NSAIDs) and theophylline. Due to the nature of the R7 side chain, FQs containing unsubstituted 7-piperazine and 7-pyrrolidine have the most significant effect. The gamma-aminobutyric acid-A (GABAA) receptor and CNS effects are inhibited through at least three possible mechanisms. Firstly, by the pharmacological action of the quinolone directly. Secondly, FQ-NSAIDs interact pharmacodynamically in which the interaction between the FQ and a receptor is significantly altered by the presence of another drug that interacts with the same receptor. An example may be the interaction between NSAIDs and some FQs. Thirdly, a pharmacokinetic drug-drug interaction leads to a higher concentration of quinolone or the other drug. An example may be the interaction between theophylline and benzodiazepines with some FQs.

Genetic characterization of hepatitis B virus genotypes among patients with chronic infection in Sulaimaniyah city, Iraq.

Background: Hepatitis B virus (HBV) genotypes are distributed unevenly throughout the world's regions. The researchers' goal in this study was to find out which HBV genotypes are now prevalent in the blood of chronic HBV patients in Iraq's Kurdistan Region's Sulaimaniyah governorate. Methods: Genotyping was carried out utilizing Polymerase Chain Reaction (PCR) type-specified primers. Thirty-three chronic HBV patients were included in the HBV genotyping assay. Phylogenic trees of Pre-S1/Pre S2/S genes' nucleotide sequences were constructed using 36 HBV isolates. Results: All the patients had HBV genotype D. Additionally, two samples were further analyzed by sequencing and deposited in GenBank as HBV/Sul-1/2021 accession numbers MZ077051 and HBV/Sul-2/2021 accession numbers MZ077052. Phylogenic analysis indicated that the HBV isolates belong to sub-genotype D1/serotype ayw2. The HBV/Sul-2/2021 had two sequence deletion mutations from G61del-T87del, which accounted for 27 amino acid deletions, and ten other mutations were identified in the carboxylic terminus of the pre-S1 from Q104del-R113del. Accordingly, 37 amino acids were deleted in the S promoter region. Several other substitution mutations were recorded in both HBV isolates. Conclusion: Patients with chronic HBV were found to have the HBV sub-genotype D1/subtype ayw2 with no mixed genotypes. HBV/Sul-1/2022, a new strain with a 37-amino acid mutation, was found to be distinct from any previously known HBV isolates.

The sub-acute toxicity of kavalactone in rats: a study of the effect of oral doses and the mechanism of toxicity in combination with ethanol.

Kava is a herbal supplement and beverage made from the Piper methysticum plant, which is known for its recreational use as a mood enhancer, relaxation, as well as pain relief for centuries. Kava is widely used among alcoholics, but it is dangerous and potentially fatal. The objectives of this study were to examine the sub-acute toxicity effects of different doses of 70% kavalactone (KL) in rats by oral application, as well as to elucidate the mechanisms of toxicity alone and in combination with ethanol (EtOH). The most common side effects observed were abnormal breathing, ataxia, lethargy, loss of appetite, indigestion, and loss of coordination, especially in the 800 mg/kg bw, po bodyweight dosage of kava treatment group alone, and in combination with EtOH. In the sub-acute study, there were dose-related decreases in body weight, feed intake, and water consumption rates. Gross and histopathological findings revealed that the liver was abnormal in color, size, consistency, and the weight significantly increased at a dose of 800 mg/kg bw, po, with KL alone and a greater increase in combination with EtOH. Hepatocellular hypertrophy (HP) and necrosis with Kupffer cells hyperplasia were observed in the periacinar zone of all rats dosed with KL (800 mg/kg bw, po) alone, and extensive changes were observed in combination with EtOH. The periportal (Z1) and mid-zonal (Z2) areas of hepatocytes were less affected as compared to the periacinar zone. These results demonstrate that EtOH exacerbated the sedative and hypnotic activity of KL, and markedly increased toxicity. The histopathological results supported the clinical and biochemical findings and the severity of hepatic damage in a dose-dependent manner.

Low vitamin D level increases women's breast cancer risks, Sulaimaniyah, Iraq: A case-control study.

Vitamin D (Vit D) is essential in maintaining calcium homeostasis and other body processes. It has been widely studied how Vit D affects cell cycle pathways and how it affects the development and prevention of breast cancer (BC). This study aimed to determine Vit D insufficiency linkage to the development of BC. In this case-control study, 130 women (65 BC patients and 65 healthy controls) aged 20-60 years who visited Shar Hospital Breast Center in Sulaimaniyah, Iraq, from December 2021 to May 2022 were included. Patients were selected after their diagnosis had been verified by breast ultrasound, mammography, and core biopsy. The ELISA test was used to measure the concentrations of serum Vit D and expressed in ng/ml. The results showed that the BC patients had considerably lower serum Vit D levels that were <20 ng/L in 66.1% (n=43) and 43.1% (n=28) in healthy controls. Compared to the control group (20.2±8.7), the mean Vit D level in BC patients was lower (17.8±8.6). A logistic regression test revealed a substantial increase in the risk of BC for low-level Vit D concentrations below 20 ng/L (OR 2.59, 95% CI 1.24-5.38; P=0.009). Vit D is still a significant risk factor for boosting the likelihood of developing BC after age and body mass index (BMI) adjustments (AOR 2.30, 95% CI 1.1-4.86; p=0.03 and AOR 3.67, 95% CI 1.55-8.7; p=0.002 for BC patients and controls, respectively). According to the outcomes of our investigations, we concluded that Vit D insufficiency raises the risk of BC among women in Sulaimaniyah, Iraq.

Correlation of SARS-CoV-2 infection severity with ABO blood groups and RhD antigen: a case-control study.

OBJECTIVE: The role of ABO types and RhD antigen in coronavirus disease 2019 (COVID-19) severity has been investigated in several recent studies. Thus, the objective of this study was to identify the relationship of ABO and RhD types with symptomatic COVID-19 disease and determine the groups associated with an increased risk of hospitalization. METHODS: This observational case-control study was performed in 530 Iraqi-Kurdish patients with COVID-19. Among them, 184 were severe cases that required hospitalization, while 346 were mild to moderate cases that were treated at home. ABO and RhD antigen groups were compared between cases and 1698 control records from 1 year before the pandemic. The diagnosis of COVID-19 was based on real-time polymerase chain reaction tests and high-resolution chest computed tomography scans with the typical clinical presentation. RESULTS: There were no significant differences in ABO and RhD antigen distributions between the COVID-19 cases and non-COVID controls. No ABO group was associated with the risk of hospitalization as a marker of the severity of infection. CONCLUSIONS: There was no significant association between symptomatic COVID-19 disease and any ABO group or RhD antigen type. No impact of ABO groups on hospitalization was documented.

Functional interplay between long non-coding RNAs and Breast CSCs.

Breast cancer (BC) represents aggressive cancer affecting most women's lives globally. Metastasis and recurrence are the two most common factors in a breast cancer patient's poor prognosis. Cancer stem cells (CSCs) are tumor cells that are able to self-renew and differentiate, which is a significant factor in metastasis and recurrence of cancer. Long non-coding RNAs (lncRNAs) describe a group of RNAs that are longer than 200 nucleotides and do not have the ability to code for proteins. Some of these lncRNAs can be mainly produced in various tissues and tumor forms. In the development and spread of malignancies, lncRNAs have a significant role in influencing multiple signaling pathways positively or negatively, making them promise useful diagnostic and prognostic markers in treating the disease and guiding clinical therapy. However, it is not well known how the interaction of lncRNAs with CSCs will affect cancer development and progression.Here, in this review, we attempt to summarize recent findings that focus on lncRNAs affect cancer stem cell self-renewal and differentiation in breast cancer development and progression, as well as the strategies and challenges for overcoming lncRNA's therapeutic resistance.

A comprehensive review about immune responses and exhaustion during coronavirus disease (COVID-19).

Coronavirus disease (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The infection was reported in Wuhan, China, in late December 2019 and has become a major global concern due to severe respiratory infections and high transmission rates. Evidence suggests that the strong interaction between SARS-CoV-2 and patients' immune systems leads to various clinical symptoms of COVID-19. Although the adaptive immune responses are essential for eliminating SARS-CoV-2, the innate immune system may, in some cases, cause the infection to progress. The cytotoxic CD8+ T cells in adaptive immune responses demonstrated functional exhaustion through upregulation of exhaustion markers. In this regard, humoral immune responses play an essential role in combat SARS-CoV-2 because SARS-CoV-2 restricts antigen presentation through downregulation of MHC class I and II molecules that lead to the inhibition of T cell-mediated immune response responses. This review summarizes the exact pathogenesis of SARS-CoV-2 and the alteration of the immune response during SARS-CoV-2 infection. In addition, we've explained the exhaustion of the immune system during SARS-CoV-2 and the potential immunomodulation approach to overcome this phenomenon. Video Abstract.

Anastasis: cell recovery mechanisms and potential role in cancer.

Balanced cell death and survival are among the most important cell development and homeostasis pathways that can play a critical role in the onset or progress of malignancy steps. Anastasis is a natural cell recovery pathway that rescues cells after removing the apoptosis-inducing agent or brink of death. The cells recuperate and recover to an active and stable state. So far, minimal knowledge is available about the molecular mechanisms of anastasis. Still, several involved pathways have been explained: recovery through mitochondrial outer membrane permeabilization, caspase cascade arrest, repairing DNA damage, apoptotic bodies formation, and phosphatidylserine. Anastasis can facilitate the survival of damaged or tumor cells, promote malignancy, and increase drug resistance and metastasis. Here, we noted recently known mechanisms of the anastasis process and underlying molecular mechanisms. Additionally, we summarize the consequences of anastatic mechanisms in the initiation and progress of malignancy, cancer cell metastasis, and drug resistance. Video Abstract.

Misdiagnosis of COVID-19 infection before molecular confirmation in Sulaimaniyah City, Iraq.

BACKGROUND: During the last 2 years, in the Kurdistan Region, Northern Iraq, there were thousands of COVID-19 cases that have not been reported officially, but diagnosed and confirmed by private laboratories and private hospitals, or clinicians based on typical clinical signs, as well as few people using home self-test after appearing of some flu-like clinical symptoms. Thus, this study aims to assess the misdiagnosis and mismanagement of cases before COVID-19 confirmation. METHODS: This study enrolled 100 consecutive patients who visited an outpatient clinic of Shar Hospital that had symptoms highly suspicious of COVID-19 infection while misdiagnosed previously to have other types of disease. Detailed questionnaires were filled for all studied patients, including age, gender, main presenting symptoms, and duration of these symptoms with the following questions: who made the false diagnosis, depending on which diagnostic test the false diagnosis was made, which medication was used for the false diagnosis, who prescribed those medications, and how long those medications were used. They were investigated by RT-PCR on their nasopharyngeal swab for confirmation. RESULTS: Most of the false diagnoses were typhoid (63%), influenza (14%), pneumonia (9%), gastroenteritis (5%), common cold (4%), brucellosis (4%), and meningitis (1%). Regarding the false diagnosis of cases, 92% were made by non-physician healthcare workers, and only 8% were made by physicians. All false diagnoses with typhoid, gastroenteritis, and common cold were made by non-physician healthcare workers, together with about half of the diagnosis of pneumonia and brucellosis, with statistically significant results (P < 0.001). CONCLUSIONS: We realized that some patients had been misdiagnosed before the COVID-19 infection confirmation. Their health conditions improved drastically after correct diagnosis and treatment, and this research is considered the first research to be conducted in Iraq in this regard.

Prospective quantitative gene expression analysis of kallikrein-related peptidase KLK10 as a diagnostic biomarker for childhood acute lymphoblastic leukemia.

Background: The most common malignancy in children is acute lymphoblastic leukemia (ALL). This study aimed to explore KLK10 mRNA expression as a potential diagnostic biomarker for ALL in children and to examine the effect of chemotherapy on KLK10 mRNA expression following the induction and after three months of receiving chemotherapy. Methods: In this prospective study, total RNA was extracted from blood samples of 23 pediatric ALL patients on diagnosis, after one month and three months of receiving chemotherapy. Healthy pediatric volunteers (n = 12) were selected as control individuals. After cDNA synthesis, KLK10 mRNA gene expression levels were quantified using quantitative real-time PCR (qRT-PCR). Results: KLK10 mRNA expression levels were significantly decreased in leukemic cells compared to their levels in cells of normal blood samples (p = 0.0001). KLK10 expression levels in ALL patients after one month and three months of receiving chemotherapy decreased compared to normal blood samples (p < 0.0001 and p = 0.0175 respectively). The expression level of KLK10 mRNA in ALL patients after one month of chemotherapy was decreased compared to their level on diagnosis (p = 0.4413). KLK10 mRNA expression levels in ALL patients after three months of chemotherapy were increased compared to their level on diagnosis (p = 0.0602). The ROC curve illustrated that KLK10 mRNA expression could very efficiently discriminate ALL patients from normal counterparts (AUC=0.886, 95% CI [0.7720-1.000], SE = 0.0582, p = 0.0004). Conclusion: KLK10 mRNA expression could serve as a potential diagnostic molecular biomarker for ALL in children.

Expression of proliferation-related genes in BM-MSC-treated ALL cells in hypoxia condition is regulated under the influence of epigenetic factors in-vitro.

Mesenchymal stem cells affect ALL cell biology under hypoxic conditions. We studied survival, proliferation, expression, and promoter methylation levels of essential genes involved in expanding MOLT-4 cells co-cultured with BM-MSC under the hypoxic condition. Here, MOLT-4 cells were co-cultured with BMMSCs under hypoxic conditions. First, the apoptosis rate was evaluated by Flow cytometry. Then, MOLT-4 cells' proliferation rate was assessed using MTT assay, and the expressions and methylation rates of genes were determined by qRT-PCR and MS-qPCR, respectively. The results showed that although MOLT-4 cells proliferation and survival rates were reduced under hypoxic conditions, this reduction was not statistically significant. Also, we showed that hypoxic conditions caused upregulation of candidate genes and affected their methylation status. Besides, it was revealed that Pontin was downregulated, while KDM3A, SKP2, and AURKA had an upward trend in the presence of MOLT-4 cells plus BM-MSC. The co-culture of leukemia cells with BMMSCs under hypoxic conditions may be a potential therapeutic approach for ALL.

Various types of electrochemical biosensors for leukemia detection and therapeutic approaches.

Leukemia often initiates following dysfunctions in hematopoietic stem cells lineages. Various types of leukemia, including acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), acute promyelocytic leukemia (APL), and human T-cell leukemia/lymphoma virus type 1 (HTLV-1) can thus call for different diagnosis and treatment options. One of the most important subjects in leukemia is the early detection of the disease for effective therapeutic purposes. In this respect, biosensors detecting the molecules of deoxyribonucleic acid (DNA) as analytes are called genosensors or DNA biosensors. Electrochemical sensors, as the most significant approach, also involve reacting of chemical solutions with sensors to generate electrical signals proportional to analyte concentrations. Biosensors can further help detect cancer cells in the early stages of the disease. Moreover, electrochemical biosensors, developed based on various nanomaterials (NMs), can increase sensitivity to the detection of leukemia-related genes, e.g., BCR/ABL as a fusion gene and promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα). Therefore, the present review reflects on previous studies recruiting different NMs for leukemia detection.

A Review on the Antiviral Activity of Functional Foods Against COVID-19 and Viral Respiratory Tract Infections.

Due to the absence of successful therapy, vaccines for protection are continuously being developed. Since vaccines must be thoroughly tested, viral respiratory tract infections (VRTIs), mainly coronaviruses, have seriously affected human health worldwide in recent years. In this review, we presented the relevant data which originated from trusted publishers regarding the practical benefits of functional foods (FFs) and their dietary sources, in addition to natural plant products, in viral respiratory and COVID-19 prevention and immune-boosting activities. As a result, FFs were confirmed to be functionally active ingredients for preventing COVID-19 and VRTIs. Furthermore, the antiviral activity and immunological effects of FFs against VRTIs and COVID-19 and their potential main mechanisms of action are also being reviewed. Therefore, to prevent COVID-19 and VRTIs, it is critical to identify controlling the activities and immune-enhancing functional food constituents as early as possible. We further aimed to summarize functional food constituents as a dietary supplement that aids in immune system boosting and may effectively reduce VRTIs and COVID-19 and promote therapeutic efficacy.

Beneficial and toxicological aspects of zinc oxide nanoparticles in animals.

Nanotechnology is a far-reaching technology with tremendous applications in various aspects, including general medicine, veterinary medicine, agriculture, aquaculture, and food production. Nanomaterials have exceptional physicochemical characteristics, including increased intestinal absorption, biodistribution, bioavailability, and improved antimicrobial and catalytic properties. Although nanotechnology is gaining ground in animal management, husbandry, and production, its wide use is still hampered by occasional toxicity and side effects. Zinc oxide nanoparticles (ZnO-NPs) have long been utilized in animal production, aquaculture, and pet animal medicine. However, the use ZnO-NPs in animals has been associated with reports of toxicity and side effects. ZnO-NPs may have shown numerous beneficial effects in animals; its use must be regulated with care to avoid unwanted consequences. Thus, this review emphasizes the usage of ZnO-NPs in animal production and laboratory animals and the potential side effects associated with the use of nanoparticles as a feed supplement and therapeutic compound.