Functional and psychosocial impact of COVID-19 pandemic on rheumatic patients’ quality of life in Saudi Arabia

Quality of Life Research - The COVID-19 pandemic might add to the stressors experienced by people living with rheumatic diseases. This study aimed to examine rheumatic patients’ functional...     

Retinal arteriovenous communication in retinitis pigmentosa with Refsum's disease-like findings

In this report we describe, herewith, a patient with primary pigmentary dystrophy of the retina (retinitis pigmentosa) associated with unilateral retinal arteriovenous communication and exudative retinal detachment. The patient had complete resolution of the retinal detachment following laser photocoagulation treatment. Such association has not been previously reported.     

Analysis of UV-induced damage and repair in young and senescent human dermal fibroblasts using the comet assay

A major cause of ageing is thought to be the accumulation of damage to macromolecules. Accumulation to DNA damage in cells therefore presupposes that aged cells are unable to repair this damage. We have used the in vitro model of cellular ageing to test the idea that senescent cells are deficient in some aspect of DNA repair. Using the alkaline single cell gel electrophoresis assay (comet assay), we have determined the responses of young and senescent human dermal fibroblasts to DNA damage caused by exposure to UVC light. At low doses of UVC, senescent cells generate smaller comets than young cells whilst at medium doses the situation is reversed. At high doses, young and senescent cells respond similarly to one another. Time course experiments revealing repair of DNA damage show that senescent cells generate larger comets than young cells at early stages of repair suggesting that either senescent cells bear more damage per genome than do young cells or that senescent cells are more efficient at excising bulky adducts from DNA. Cells maintained in low levels of serum irrespective of age are less able to repair DNA damage compared with cells maintained in high levels of serum, and furthermore young and senescent cells maintained in high levels of serum are equally able to repair DNA damage. Our data, therefore, reveal both age-dependent and age-independent responses to UV-induced DNA damage. Use of the comet assay highlights the heterogeneity of cellular responses to genotoxic stress.     

Use of PCR for Diagnosis of Post-Kala-Azar Dermal Leishmaniasis

Microscopy and PCR were compared for use in the diagnosis of post-kala-azar dermal leishmaniasis (PKDL) in 63 patients. Aspirates of lymph nodes (samples from 52 patients), skin (23 samples), and bone marrow (18 samples) were used. For 11 patients lymph node aspiration could be repeated 6 months after they recovered from PKDL. During active PKDL, PCR was positive for 42 of 52 (80.8%) lymph node aspirates and 19 of 23 (82.7%) skin aspirates, whereas microscopy was positive for only 9 of 52 (17.3%) lymph node aspirates and 7 of 23 (30.4%) skin aspirates. PCR was always positive when parasites were seen by microscopy. When the results obtained with lymph node and skin aspirates from the same patient (n = 16) were compared, there was complete agreement. Bone marrow samples were negative by microscopy and PCR for 16 patients and positive by both methods for 1 patient; for one sample only the PCR was positive. PCR confirmed the co-occurrence of visceral leishmaniasis and PKDL in one patient and confirmed the suspicion of this co-occurrence in the other patient. After recovery, no parasites were found by microscopy, but 2 of 11 (18.2%) samples were still positive by PCR. Thirty negative controls were all found to be PCR negative, and 15 positive controls were all PCR positive. Cross-reactions with Mycobacterium leprae could be ruled out. In conclusion, PCR with inguinal lymph node or skin aspirates is suitable for confirming the clinical diagnosis of PKDL. In some patients, lymph node aspirates are probably preferred because aspiration of material from the skin may leave scars.     

Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation

Motility of unicellular organisms occurred early in evolution with the emergence of cilia and flagella. In vertebrates, motile cilia are required for numerous functions such as clearance of the airways and determination of left-right body asymmetry. Ependymal cells lining the brain ventricles also carry motile cilia, but their biological function has remained obscure. Here, we show that ependymal cilia generate a laminar flow of cerebrospinal fluid through the cerebral aqueduct, which we term as 'ependymal flow'. The axonemal dynein heavy chain gene Mdnah5 is specifically expressed in ependymal cells, and is essential for ultrastructural and functional integrity of ependymal cilia. In Mdnah5-mutant mice, lack of ependymal flow causes closure of the aqueduct and subsequent formation of triventricular hydrocephalus during early postnatal brain development. The higher incidence of aqueduct stenosis and hydrocephalus formation in patients with ciliary defects proves the relevance of this novel mechanism in humans.     

Dominant negative mutations in the C-propeptide of COL2A1 cause platyspondylic lethal skeletal dysplasia, torrance type, and define a novel subfamily within the type 2 collagenopathies

Platyspondylic lethal skeletal dysplasia (PLSD) Torrance type (PLSD-T) is a rare skeletal dysplasia characterized by platyspondyly, brachydactyly, and metaphyseal changes. Generally a perinatally lethal disease, a few long-term survivors have been reported. Recently, mutations in the carboxy-propeptide of type II collagen have been identified in two patients with PLSD-T, indicating that PLSD-T is a type 2 collagen-associated disorder. We studied eight additional cases of PLSD-T and found that all had mutations in the C-propeptide domain of COL2A1. The mutational spectrum includes missense, stop codon and frameshift mutations. All non-sense mutations were located in the last exon, where they would escape non-sense-mediated RNA-decay. We conclude that PLSD-T is caused by mutations in the C-propeptide domain of COL2A1, which lead to biosynthesis of an altered collagen chain (as opposed to a null allele). Similar mutations have recently been found to be the cause of spondyloperipheral dysplasia, a non-lethal dominant disorder whose clinical and radiographical features overlap those of the rare long-term survivors with PLSD-T. Thus, spondyloperipheral dysplasia and PLSD-T constitute a novel subfamily within the type II collagenopathies, associated with specific mutations in the C-propeptide domain and characterized by distinctive radiological features including metaphyseal changes and brachydactyly that set them apart from other type 2 collagenopathies associated with mutations in the triple-helical domain of COL2A1. The specific phenotype of C-propeptide mutations could result from a combination of diminished collagen fibril formation, toxic effects through the accumulation of unfolded collagen chains inside the chondrocytes, and alteration of a putative signaling function of the carboxy-propeptide of type 2 collagen.     

Methimazole in the Treatment of Melasma: A Clinical and Dermascopic Study

BACKGROUND: Melasma is a chronic hypermelanotic disorder that is challenging to treat; no single effective therapeutic agent for it has been discovered. Methimazole, an oral antithyroid drug, has a skin depigmenting effect when used topically. OBJECTIVE: We sought to evaluate the efficacy and safety of methimazole, applied during microneedling sessions and additional topical use in between sessions, for the treatment of melasma. METHODS: This split-face study included 30 Egyptian patients with melasma, each of whom received 12 microneedling sessions once per week for 12 weeks followed by topical methimazole on the right side of face and placebo on the left side. In between the sessions, topical methimazole 5% cream was applied twice per day on the right side and placebo on the left side. Assessments were performed using the Hemi-melasma Area and Severity Index (hemi-MASI) percentage of improvement, patient satisfaction, dermoscopy, and thyroid-stimulating hormone (TSH) serum levels. RESULTS: There were significant clinical and dermoscopic improvements; hemi-MASI scores on the methimazole-treated right sides were decreased (p<0.001). The percent of hemi-MASI score improvement was significantly associated with the malar pattern (p=0.031) and epidermal type (p=0.04) of melasma. About 70 percent of our studied patients reported being satisfied with their treatment response (7% excellent, 33% good, 30% fair). No significant local or systemic side effects were observed. Pre- and posttreatment serum TSH levels were within the normal range in all treated cases. CONCLUSIONS: Methimazole has the potential to be a safe and promising therapeutic agent for the treatment of melasma via dermapen-delivered microneedling sessions with topical use in between sessions.     

Antibacterial macrolides: a drug class with a complex pharmacological profile.

Macrolides are widely used antibacterial agents. Although generally well tolerated, they have a number of important additional pharmacological effects, which can sometimes result in significant adverse reactions. This review focuses on three of these side effects: the prokinetic action associated with stimulation of motilin receptors, the proarrhythmic effect due to prolongation of the QT interval of the electrocardiogram and the potential for drug interactions due to inhibition of drug metabolising enzymes. For macrolides that have obtained marketing authorisation in Italy, United Kingdom or United States of America, we also considered whether these actions are properly reported in the approved summaries of the product characteristics and tried to provide strategies to identify patients at risk of significant side effects when macrolides are administered.     

Mother's dietary diversity and association with stunting among children <2 years old in a low socio‐economic environment: A case–control study in an urban care setting in Dhaka,Bangladesh

Mothers are often responsible for preparing nutritious foods in their households. However, the quality of mother's diets is often neglected, which may affect both mother's and child's nutrition. Because no single food contains all necessary nutrients, diversity in dietary sources is needed to ensure a quality diet. We aimed to study the association between mother's dietary diversity and stunting in children <2 years attending Dhaka Hospital of icddr,b, a diarrhoeal disease hospital in Dhaka, Bangladesh. A case–control study (n = 296) was conducted from November 2016 to February 2017. Data were collected from mothers of stunted children <2 years (length‐for‐age z score [LAZ] < ?2) as “cases” and nonstunted (LAZ ≥ ?1) children <2 years as “controls.” Mothers were asked to recall consumption of 10 defined food groups 24 hr prior to the interview as per Guidelines for Minimum Dietary Diversity for Women. Among the mothers of cases, 58% consumed <5 food groups during the last 24 hr, compared with 45% in control mothers (P = 0.03). Children whose mothers consumed <5 food groups were 1.7 times more likely to be stunted than children whose mothers consumed ≥5 food groups (P = 0.04). Intake of food groups such as pulses, dairy, eggs, and vitamin A rich fruit was higher in control mothers. Proportion of mother's illiteracy, short stature, monthly family income <BDT 11,480, absence of bank account, and poor sanitation was also found to be higher in stunted group. Further study particularly intervention or longitudinal study to see the causality of mother's dietary diversity with child stunting is recommended.     

Improved recovery profiles in sinonasal surgery Sugammadex: Does it have a role?

ObjectiveSinonasal surgery is one of the shared airway surgeries that are not uncommonly complicated intra or postoperatively. The proper anesthetic management of these cases plays a crucial role creating a bloodless field. Sugammadex is a new selective relaxant binding drug as it provides a rapid decrease in free rocuronium in the plasma and at nicotinic receptor that help proper awakening of these patients which is extremely important for minimizing the postoperative respiratory complications. The aim of this study is to compare recovery profile in sinonasal surgery in patients reversed by conventional anticholine esterase (Neostigmine) versus those reversed by Sugammadex.MethodsThis study included 40 patients ASA physical status I and II aged 20–45 years with chronic sinusitis undergoing endoscopic sinus surgery with or without septoplasty, hypotensive anesthesia to maintain MAP (50–60 mm Hg), muscle relaxation throughout the procedure at 1–2 posttetanic count (PTCs) by rocuronium infusion, and anesthetic depth maintained using BIS (50–60). Patients were allocated randomly into two equal groups to receive either Sugammadex 4 mg/kg (group I) or Neostigmine 0.05 mg/kg and atropine 0.02 mg/kg (group II) as a reversal agent, and assessment of postoperative respiratory complications was performed using the Postoperative Respiratory System Evaluation Score (PRSES) at 1st and 5th minutes after extubation.ResultsThe reversal time showed highly significant difference between the two groups. Patients in the Sugammadex group could reach a TOF of 0.9 in a mean time 2.47 (0.51) min versus 24.21 (4.7) min for the Neostigmine group; postoperative respiratory complications, the Sugammadex group and the Neostigmine group did not differ statistically; however, more patients in Neostigmine group showed respiratory complications at 1st and 5th minutes after extubation as shown by PRSES Scoring System.ConclusionThis study showed that the use of Sugammadex in reversing rocuronium induced neuromuscular block in patients undergoing functional endoscopic surgery is superior to Neostigmine. Further studies are required to weigh the cost benefit relationship of the use of Sugammadex in routine clinical practice.