C5 Complement Deficiency in a Saudi Family, Molecular Characterization of Mutation and Literature Review

Introduction

Complement deficiencies are rare primary immunodeficiency disorders, the diagnosis of which is often underestimated. Only a small number of molecular studies have been carried out for the characterization of the underlying genetic defects in these cases.

Purpose

Reporting the first family from the Arabian Gulf region with multiple members affected by meningococcemia and abscent serum complement 5 (C5). We tried to correlate clinical, biochemical and molecular genetics features of this family.

Methods

Determination of the serum level of all complement proteins including the terminal cascade (C5-9), followed by mutation analysis on DNA extracted from fresh blood samples of each alive family member.

Results

Molecular studies showed a homozygous nonsense mutation in exon 1, with the change of cytosine to thymine at position 55 (55C > T) leading to change of the glutamine amino acid at position 19 to a stop codon (Q19X), and serologically absence of C5 in the serum. A similar but compound heterozygous mutation has been reported in one African–American family. previously.

Conclusion

Characterization of the underlying mutations in C5 deficient families is important, to understand this uncommon complement deficiency, and try to elucidate structure–function relationships in the C5 gene. This report also highlights the importance of complement screening in cases of sporadic meningococcal Infections, especially in communities with high prevalence of consanguineous marriages, which will ensure timely and adequate clinical interventions.     

Containment of Local COVID-19 Outbreak Among Hematopoietic Stem Cell Transplant Recipients and Healthcare Workers in a Pediatric Stem Cell Unit

Journal of Clinical Immunology -     

Factors associated with violence against women in a representative sample of the Lebanese population: results of a cross-sectional study

To evaluate the prevalence of violence against women (VAW) and assess factors associated with VAW among a representative sample of the Lebanese population. This cross-sectional study was carried out between September and December 2018. Participants from all Lebanese governorates were enrolled in this study using a proportionate random sample. The percentages of women who were exposed to physical and non-physical abuse were 37.1% and 49.4% respectively. Factors associated with physical abuse were being divorced, having a partner addicted to substances and alcohol, or with a history of threats, violence, assaults, and crimes, higher stressful life experiences, and abuse reported from childhood (physical, sexual, or psychological). Non-physical abuse was associated with abuse reported from childhood (physical, sexual, or psychological), higher stressful life experiences, and the fact that the partner is addicted to substances and alcohol, or has a history of threats. Our results suggest that being divorced, illiterate, and unemployed, having an addicted partner, and having experienced child abuse are all factors that are associated with more violence against women.

     

Antifibrotic effect of aloe vera in viral infection-induced hepatic periportal fibrosis

AIM: To investigate the anti-oxidative and anti-fibrotic effects of aloe vera in patients with liver fibrosis.METHODS: Aloe vera high molecular weight fractions (AHM) were processed by patented hyper-dry system in combination of freeze-dry technique with microwave and far infrared-ray radiation. Fifteen healthy volunteers as the control group and 40 patients were included. The patients were randomly subdivided into two equal groups: the conventional group was treated with placebo (starch), and AHM group was treated with 0.15 gm/d AHM, both for 12 consecutive weeks. The patients were investigated before and after treatment. Serum activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), hyaluronic acid (HA), transforming growth factor-β (TGF-β) and matrixmetalloproteinase-2 (MMP-2) were determined. The reduced glutathione (GSH) and malondialdehyde (MDA) levels in liver were assayed and the expression of hepatic α-smooth muscle actin (α-SMA) was identified by immunohistochemistry.RESULTS: At the start of the study, the hematoxylin and eosin staining revealed fibro-proliferated bile ductules, thick fibrous septa and dense inflammatory cellular infiltration in the patients before treatment. The use of AHM for 12 wk significantly ameliorated the fibrosis, inhibited the inflammation, and resulted in minimal infiltration and minimal fibrosis compared to the conventional group. The enzyme activities of the liver (ALT, AST and ALP) were attenuated after treatment in both groups, and the decrease in the AHM group was more significant as compared with the conventional group. Similar to the AST, the MDA levels were significantly higher before treatment, and were attenuated after treatment in both groups. In contrast, the hepatic glutathione content in the patients were decreased significantly in the AHM group compared to the controls. The serum levels of the fibrosis markers (HA, TGF-β and MMP-2) were also reduced significantly after treatment. The expression of α-SMA was modified in patients before and after treatment as compared with the normal controls. In the conventional group, there was only thin and incomplete parenchymal α-SMA positive septum joining the thickened centrilobular veins, while in the AHM group, few α-SMA positive cells were present in sinusoid and lobule after treatment.CONCLUSION: Oral supplementation with AHM could be helpful in alleviating the fibrosis and inflammation of hepatic fibrosis patients.     

Manipulating the drug/proton antiport stoichiometry of the secondary multidrug transporter MdfA

Multidrug transporters are integral membrane proteins that use cellular energy to actively extrude antibiotics and other toxic compounds from cells. The multidrug/proton antiporter MdfA from Escherichia coli exchanges monovalent cationic substrates for protons with a stoichiometry of 1, meaning that it translocates only one proton per antiport cycle. This may explain why transport of divalent cationic drugs by MdfA is energetically unfavorable. Remarkably, however, we show that MdfA can be easily converted into a divalent cationic drug/≥2 proton-antiporter, either by random mutagenesis or by rational design. The results suggest that exchange of divalent cationic drugs with two (or more) protons requires an additional acidic residue in the multidrug recognition pocket of MdfA. This outcome further illustrates the exceptional promiscuous capabilities of multidrug transporters.     

Analgesic efficacy and outcome of transversus-abdominis plane block versus low thoracic-epidural analgesia after laparotomy in ischemic heart disease patients

Background

Tranversus-abdominis plane (TAP) block is a novel technique alternative to central neural blockade in providing analgesia to the anterior abdominal wall. As such, we compared the analgesic efficacy of TAP block with low thoracic-epidural analgesia (TEA) in ischemic heart disease patients after abdominal laparotomy.

Methods

Forty-four American Society of Anesthesiologists physical status (ASA) III patients, 59–75 years of age and undergoing elective upper abdominal surgery under general anesthesia, were assigned randomly to receive either continuous low TEA or intermittent administration of local anesthetic in TAP block. Supplemental analgesia was provided with intravenous morphine with patient-controlled-analgesia. Morphine consumption and pain intensity using verbal rating scale (VRS) at rest and coughing over the first 48 h were recorded.

Results

Whereas all patients in the TAP group required morphine, 16 (72.2 %) patients in TEA group received morphine postoperatively (p = 0.021). Morphine consumed on day 1 and day 2 was 11.5 mg (7.5–12.3 mg) and 7mg (4.5–8 mg) for the TEA group, while in the TAP group, it was 18 mg (16–19 mg) and 11 mg (10–13 mg), respectively (p < 0.001). Time for first request of morphine was 311.2 ± 18.5 min in the TEA group versus 210 ± 22.2 min in the TAP group (p < 0.001). VRS at rest and cough were lower in the TEA group compared with the TAP group at 1, 6, 12, 18, 24, 36 and 48 h (p < 0.001). Incidence of hypotension and ephedrine administration were significantly higher in the TEA group than in the TAP group (p = 0.007).

Conclusion

Low TEA reduced morphine consumption and provided a higher analgesic efficacy compared with TAP block after laparotomy in ischemic heart disease patients.     

Occupational exposure to second hand smoke and respiratory and sensory symptoms: A cross-sectional survey of hospital workers in Egypt

Objective

Exposure to Second Hand Smoke (SHS) has been associated with an increased risk of respiratory symptoms, upper and lower respiratory tract diseases and an increased risk of asthma and chronic obstructive pulmonary disease. The majority of cases of mortality and morbidity is attributable to exposure of adults to SHS and is related to cardiovascular diseases and lung cancer. In Egypt, comprehensive smoke-free laws exist, however, in many workplaces they are poorly enforced consequently exposing workers to the detrimental health hazards of SHS. We aimed at determination of workplace exposure to Second Hand Smoke (SHS) and its association with respiratory and sensory irritation symptoms in hospital workers in Port-said governorate in Egypt.

Material and Methods

A cross-sectional face to face survey was conducted by the use of a standardised questionnaire among 415 adult hospital workers; representing 50% of all employees (81% response rate); recruited from 4 randomly selected general hospitals in Port-said governorate in Egypt.

Results

All hospitals employees reported exposure to SHS — on average 1.5 (SD = 2.5) hours of exposure per day. After controlling for potential confounders, exposure to SHS at work was significantly associated with an increased risk of wheezes (OR = 1.14, p < 0.01), shortness of breath (OR = 1.17, p < 0.01), phlegm (OR = 1.23, p < 0.01), running and irritated nose (OR = 1.14, p < 0.01) as well as a sore, scratchy throat (OR = 1.23).

Conclusions

These findings point out that workplace exposure to SHS is evident in hospitals in Port-said governorate and that workers are adversely affected by exposure to it at work. This underlines the importance of rigorous enforcement of smoke-free policies to protect the workers’ health in Egypt.     

In vitro assessment of the bioactivities of sericin protein extracted from a bacterial silk-like biopolymer

Sericin is one of the main components of silk proteins, which has numerous biomedical applications because of its antioxidant, anticancer and antimicrobial properties. We recently isolated and characterized a novel silk-like protein named BNES. It is of non-animal origin and is like a bacterial polymeric silk. Sericin is a very popular protein compound that is effective in treating cancerous tumors. The process of extracting it from natural silk produced by silkworms or spiders is both complex and expensive. From the published scientific literature, it has been shown that sericin has not been previously extracted from a bacterial source. In the present study, sericin was extracted from bacteria capable of producing a biopolymer named BNES whose chemical composition is like that of natural silk and its bio-therapeutic effects were evaluated for the first time. The antioxidant activity of BNES measured by DPPH and ABTS assays showed IC₅₀ values of 0.38 and 0.41 mg mL⁻¹, respectively. BNES displayed satisfactory cytotoxic effect against four cancer cell lines, including Huh-7, Caco-2, MCF-7 and A549 cells, with IC₅₀ values in the ranges of ca. 0.62 ± 0.17, 0.72 ± 0.27, 0.76 ± 0.36 and 0.83 ± 0.31 mg mL⁻¹, respectively, after 24 h of treatment and 0.51 ± 0.22, 0.49 ± 0.19, 0.41 ± 0.25 and 0.55 ± 0.38, respectively, after 48 h of treatment, without affecting normal cells (WI38 cells). The antitumor activity of BNES was established to be an apoptosis-dependent mechanism determined via cellular morphology alterations, cell cycle arrest in the sub-G1 phase and nuclear staining with highly fluorescent fragments. The antimicrobial effects of BNES were examined with yeast and Gram-negative and Gram-positive bacteria. The results confirmed its antimicrobial activity against all tested organisms at concentrations of up to 1.33 mg mL⁻¹. The competitive advantage of the bacterial sericin BNES over sericin extracted from spider or silkworm sources is that it can be produced in very large quantities through large-scale bio-fermenters, which reduces the expected cost of production, in addition to having sustainable bacterial production source.

Sericin is one of the main components of silk proteins, which has numerous biomedical applications because of its antioxidant, anticancer and antimicrobial properties.     

Machine learning-based LIBS spectrum analysis of human blood plasma allows ovarian cancer diagnosis

Early-stage screening and diagnosis of ovarian cancer represent an urgent need in medicine. Usual ultrasound imaging and cancer antigen CA-125 test when prescribed to a suspicious population still require reconfirmations. Spectroscopic analyses of blood, at the molecular and atomic levels, provide useful supplementary tests when coupled with effective information extraction methods. Laser-induced breakdown spectroscopy (LIBS) was employed in this work to record the elemental fingerprint of human blood plasma. A machine learning data treatment process was developed combining feature selection and regression with a back-propagation neural network, resulting in classification models for cancer detection among 176 blood plasma samples collected from patients, including also ovarian cyst and normal cases. Cancer diagnosis sensitivity and specificity of respectively 71.4% and 86.5% were obtained for randomly selected validation samples.