Displaying publications 181 - 200 of 330 in total

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  1. Rosharudin NA, Muhammad NA, Mohd Daud TI, Hoesni SM, Yusoff SR, Razman MOI, et al.
    PLoS One, 2023;18(8):e0289551.
    PMID: 37639447 DOI: 10.1371/journal.pone.0289551
    OBJECTIVE: The Difficulties in Emotion Regulation Scale-18 (DERS-18) is an instrument used to measure deficits in emotion regulation. However, the instrument has not been adapted to Malaysians and has never been validated in the Malay language. This study aimed to examine the psychometric properties of the Malay version of DERS-18.

    METHOD: The DERS-18 underwent forward-backward translation and assessment of face and content validity. Both Malay version of the DERS-18 and DASS-21 were completed by 701 adolescents (44.4% boys) aged 13 and 14 years old. To assess its dependability, a floor and ceiling effect evaluation and Cronbach's analysis were both performed. A series of confirmatory factor analyses (CFA), bivariate correlation, and regression were performed to evaluate the construct and criterion validity, respectively.

    RESULTS: The Malay version of DERS-18, after excluding "Awareness", indicated excellent reliability (Cronbach's α = 0.93), and acceptable internal consistency for each subscale (range of α from 0.63 to 0.82). Floor or ceiling effects were observed at item level and subscale level, but not at total level. CFA results revealed that the Malay version of the DERS-18 bifactor model (excluding "Awareness") portrayed the best construct validity (χ2/df = 2.673, RMSEA = 0.049, CFI = 0.977, TLI = 0.968) compared to a single factor, a correlated factor, and a higher-order factor model. The DERS-18 subscales (except "Awareness") and DERS-18 total scores were significantly correlated with stress, anxiety, and depression in a positive direction (r ranged from 0.62 to 0.64, p < 0.01). The general factor of the DERS-18 and its specific factors ("Clarity", "Goals", and "Non-Acceptance") significantly predicted the symptoms of stress, anxiety, and depression (R2 ranged from 0.44 to 0.46, p < 0.001).

    CONCLUSION: The Malay version of the DERS-18, excluding "Awareness", possessed good reliability, construct validity, and criterion validity to assess emotion dysregulation among Malaysian adolescents.

  2. Tao H, Jawad AH, Shather AH, Al-Khafaji Z, Rashid TA, Ali M, et al.
    Environ Int, 2023 May;175:107931.
    PMID: 37119651 DOI: 10.1016/j.envint.2023.107931
    This study uses machine learning (ML) models for a high-resolution prediction (0.1°×0.1°) of air fine particular matter (PM2.5) concentration, the most harmful to human health, from meteorological and soil data. Iraq was considered the study area to implement the method. Different lags and the changing patterns of four European Reanalysis (ERA5) meteorological variables, rainfall, mean temperature, wind speed and relative humidity, and one soil parameter, the soil moisture, were used to select the suitable set of predictors using a non-greedy algorithm known as simulated annealing (SA). The selected predictors were used to simulate the temporal and spatial variability of air PM2.5 concentration over Iraq during the early summer (May-July), the most polluted months, using three advanced ML models, extremely randomized trees (ERT), stochastic gradient descent backpropagation (SGD-BP) and long short-term memory (LSTM) integrated with Bayesian optimizer. The spatial distribution of the annual average PM2.5 revealed the population of the whole of Iraq is exposed to a pollution level above the standard limit. The changes in temperature and soil moisture and the mean wind speed and humidity of the month before the early summer can predict the temporal and spatial variability of PM2.5 over Iraq during May-July. Results revealed the higher performance of LSTM with normalized root-mean-square error and Kling-Gupta efficiency of 13.4% and 0.89, compared to 16.02% and 0.81 for SDG-BP and 17.9% and 0.74 for ERT. The LSTM could also reconstruct the observed spatial distribution of PM2.5 with MapCurve and Cramer's V values of 0.95 and 0.91, compared to 0.9 and 0.86 for SGD-BP and 0.83 and 0.76 for ERT. The study provided a methodology for forecasting spatial variability of PM2.5 concentration at high resolution during the peak pollution months from freely available data, which can be replicated in other regions for generating high-resolution PM2.5 forecasting maps.
  3. Talab F, Alam A, Zainab, Ullah S, Elhenawy AA, Shah SAA, et al.
    J Biomol Struct Dyn, 2024 Feb 22.
    PMID: 38385366 DOI: 10.1080/07391102.2024.2319677
    This research work reports the synthesis of new derivatives of the hydrazone Schiff bases (1-17) based on polyhydroquinoline nucleus through multistep reactions. HR-ESIMS,1H- and 13C-NMR spectroscopy were used to structurally infer all of the synthesized compounds and lastly evaluated for prolyl oligopeptidase inhibitory activity. All the prepared products displayed good to excellent inhibitory activity when compared with standard z-prolyl-prolinal. Three derivatives 3, 15 and 14 showed excellent inhibition with IC50 values 3.21 ± 0.15 to 5.67 ± 0.18 µM, while the remaining 12 compounds showed significant activity. Docking studies indicated a good correlation with the biochemical potency of compounds estimated in the in-vitro test and showed the potency of compounds 3, 15 and 14. The MD simulation results confirmed the stability of the most potent inhibitors 3, 15 and 14 at 250 ns using the parameters RMSD, RMSF, Rg and number of hydrogen bonds. The RMSD values indicate the stability of the protein backbone in complex with the inhibitors over the simulation time. The RMSF values of the binding site residues indicate that the potent inhibitors contributed to stabilizing these regions of the protein, through formed stable interactions with the protein. The Rg. analysis assesses the overall size and compactness of the complexes. The maintenance of stable hydrogen bonds suggests the existence of favorable binding interactions. SASA analysis suggests that they maintained stable conformations without large-scale exposure to the solvent. These results indicate that the ligand-protein interactions are stable and could be exploited to design new drugs for disease treatment.Communicated by Ramaswamy H. Sarma.
  4. Naqvi AA, Hassali MA, Rizvi M, Zehra A, Nisa ZU, Islam MA, et al.
    Front Pharmacol, 2020;11:1039.
    PMID: 32765264 DOI: 10.3389/fphar.2020.01039
    Objective: The aim was to validate the Urdu version of General Medication Adherence Scale (GMAS) in patients with rheumatoid arthritis disease.

    Methods: A 2-month (March-April 2019) cross-sectional study was conducted in randomly selected out-patients with rheumatoid arthritis. The sample size was calculated using item-subject ratio of 1:20. The scale was evaluated for factorial, concrete, concurrent, and known group validities. Concrete validity was established by correlating scores of EQ-5D quality of life scale and GMAS adherence score. Concurrent validity was established by correlating the GMAS adherence score with pill count. Analyses for sensitivity were also conducted. Cut-off value was determined through receiver operator curve (ROC), and test-retest method was used to analyze internal consistency and reliability. Data were analyzed through IBM SPSS, IBM AMOS, and MedCalc software. The Urdu version of EQ-5D quality of life questionnaire was used with permission from developers (#ID20884). The study was approved by an ethics committee (#NOV:15).

    Results: A total of 351 responses were analyzed. The response rate was 98%. Reliability was in acceptable range, i.e., Cronbach α = 0.797. Factorial validity was established by calculation of satisfactory fit indices. Correlation coefficients for concrete and concurrent validities were ρ = 0.687, p < 0.01 and ρ = 0.779, p < 0.01, respectively. Known group validity was established as significant association of adherence score with insurance and illness duration (p < 0.05) that were reported. Sensitivity of the scale was 94%. Most patients had high adherence (N = 159, 45.3%).

    Conclusion: The Urdu version of GMAS demonstrated adequate internal consistency and was validated. These results indicate that it is an appropriate tool to measure medication adherence in Pakistani patients with rheumatoid arthritis.

  5. Haseeb A, Faidah HS, Al-Gethamy M, Iqbal MS, Alhifany AA, Ali M, et al.
    Saudi Pharm J, 2020 Oct;28(10):1166-1171.
    PMID: 33132709 DOI: 10.1016/j.jsps.2020.08.005
    Antimicrobial stewardship programs (ASPs) are collaborative efforts to optimize antimicrobial use in healthcare institutions through evidence-based quality improvement strategies. The general administration of pharmaceutical care in the Saudi ministry of health (MOH) is putting outstanding efforts in implementing antimicrobial stewardship in Saudi health care settings. Several surveys have been conducted globally and reported many types of antimicrobial stewardship strategies in health institutions and their effectiveness. This study aims to identify ASPs in Makkah region hospitals and their perceived level of success. We administered a regional survey to explore current progress and issues related to the implementation of ASPs in Makkah region hospitals at the pharmacy level (n = 25). Among responding hospitals, 19 (76%) hospitals, the most commonly reported ASP were as following: formulary restrictions (90%) for broad-spectrum antimicrobials and use of prospective feedback on antimicrobial prescribing (68%), use of clinical guidelines and pathways (100%), and use of automatic stop orders (68%) to limit inappropriate antimicrobial therapy. The study outcomes will also be of pivotal importance to devise policies and strategies for antimicrobial stewardship implementation in other non-MOH settings in the Makkah region. Based on our results, all reported institutions have at least one antimicrobial stewardship program in a process with a high success rate. A multidisciplinary ASP approach, active involvement of drug & therapeutic committee, formulary restrictions, and availability of education & training of pharmacists and physicians on ASP are the primary elements for perceived successful antimicrobial stewardship programs in the Makkah region hospitals.
  6. AlShayban DM, Naqvi AA, Alhumaid O, AlQahtani AS, Islam MA, Ghori SA, et al.
    Front Pharmacol, 2020;11:60.
    PMID: 32153397 DOI: 10.3389/fphar.2020.00060
    Objective: The study aimed to evaluate the association between disease knowledge and medication adherence in patients with type 2 diabetes mellitus.

    Methods: A cross-sectional study was conducted for three months, in patients with type 2 diabetes who visited three community pharmacies located in Khobar, Saudi Arabia. Patients' disease knowledge and their adherence to medications were documented using Arabic versions of the Michigan Diabetes Knowledge Test and the General Medication Adherence Scale respectively. Data were analyzed through SPSS version 23. Chi-square test was used to report association of demographics with adherence. Spearman's rank correlation was employed to report the relationship among HbA1c values, disease knowledge and adherence. Logistic regression model was utilized to report the determinants of medication adherence and their corresponding adjusted odds ratio. Study was approved by concerned ethical committee (IRB-UGS-2019-05-001).

    Results: A total of 318 patients consented to participate in the study. Mean HbA1c value was 8.1%. A third of patients (N = 105, 33%) had high adherence and half of patients (N = 162, 50.9%) had disease knowledge between 51% - 75%. A significantly weak-to-moderate and positive correlation (ρ = 0.221, p < 0.01) between medication adherence and disease knowledge was reported. Patients with >50% correct answers in the diabetes knowledge test questionnaire were more likely to be adherent to their medications (AOR 4.46, p < 0.01).

    Conclusion: Disease knowledge in most patients was average and half of patients had high-to-good adherence. Patients with better knowledge were 4 to 5 times more likely to have high adherence. This highlights the importance of patient education and awareness regarding medication adherence in managing diabetes.

  7. Ali N, Nur Kalmi Z, Sanusi NS, Ahad A, Mohd Khairuddin NA, Rosman SR, et al.
    Malays Fam Physician, 2022 Nov 30;17(3):137-143.
    PMID: 36606167 DOI: 10.51866/oa.135
    INTRODUCTION: Anaemia is common during pregnancy and can lead to miscarriage, intrauterine growth retardation, premature labour and antepartum haemorrhage. Anaemia in pregnancy is defined as a haemoglobin (Hb) level of <11 g/dL.

    METHOD: This retrospective review included 407 antenatal mothers diagnosed with anaemia at 36±1 weeks of gestation at all 10 health clinics in Alor Gajah between January and December 2018.

    RESULTS: According to the district annual returns, 2,407 antenatal mothers (36 weeks of gestation) were registered in the health clinics in Alor Gajah in 2018. Among them, the prevalence of anaemia was 18.6% (n=448). However, there were only 407 cards found. Most participants were Malays (89.4%), aged 20-40 years (93.6%) and married (96.3%). Almost all anaemia cases (96.5%) were mild (Hb level of 9-10.9 g/dL). Approximately 34.4% of the mothers were already anaemic at booking; 77.6% belonged to the B40 income group; and 31.6% had poor pregnancy spacing of <2 years. Iron deficiency anaemia was the most common type of anaemia (51.0%), followed by dilutional anaemia (34.0%), which did not normalise at 36 weeks of gestation. Anaemia was associated with lower educational (p<0.05) and Hb levels at booking (p<0.001).

    CONCLUSION: Having normal maternal Hb levels in early pregnancy especially at booking is crucial, as it may reduce the possibility of anaemia during pregnancy. Early screening and supplementation of at-risk pregnancies may be applied as a preventive strategy. Suitable methods of iron treatment and investigation need further exploration.

  8. Liu X, Yunus Y, Lu D, Aghakhanian F, Saw WY, Deng L, et al.
    Hum Genet, 2015 Apr;134(4):375-92.
    PMID: 25634076 DOI: 10.1007/s00439-014-1525-2
    The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, continue to adopt an agro-subsistence nomadic lifestyle, residing primarily within natural jungle habitats. Leading a hunter-gatherer lifestyle in a tropical jungle environment, the Orang Asli are routinely exposed to malaria. Here we surveyed the genetic architecture of individuals from four Orang Asli tribes with high-density genotyping across more than 2.5 million polymorphisms. These tribes reside in different geographical locations in Peninsular Malaysia and belong to three main ethno-linguistic groups, where there is minimal interaction between the tribes. We first dissect the genetic diversity and admixture between the tribes and with neighboring urban populations. Later, by implementing five metrics, we investigated the genome-wide signatures for positive natural selection of these Orang Asli, respectively. Finally, we searched for evidence of genomic adaptation to the pressure of malaria infection. We observed that different evolutionary responses might have emerged in the different Orang Asli communities to mitigate malaria infection.
  9. Mengesha MG, Rajasekaran S, Ramachandran K, Sengodan VC, Yasin NF, Williams LM, et al.
    J Orthop, 2024 Sep;55:97-104.
    PMID: 38681829 DOI: 10.1016/j.jor.2024.04.018
    PURPOSE: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care.

    METHODS: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East). Patients who developed orthopedic surgical site infection between January 2021 and December 2022 were included. Demographic details, bacterial profile of surgical site infection, and antibiotic sensitivity pattern were documented.

    RESULTS: 2038 patients from 24 countries were included. Among them 69.7 % were male patients and 64.1 % were between 20 and 60 years. 70.3 % patients underwent trauma surgery and instrumentation was used in 93.5 %. Ceftriaxone was the most common preferred in 53.4 %. Early SSI was seen in 55.2 % and deep SSI in 59.7 %. Western Africa (76 %) and Asia-Pacific (52.8 %) reported a higher number of gram-negative infections whereas gram-positive organisms were predominant in other regions. Most common gram positive organism was Staphylococcus aureus (35 %) and gram-negative was Klebsiella (17.2 %). Majority of the organisms showed variable sensitivity to broad-spectrum antibiotics.

    CONCLUSION: Our study strongly proves that every institution has to analyse their surgical site infection microbiological profile and antibiotic sensitivity of the organisms and plan their surgical antimicrobial prophylaxis accordingly. This will help to decrease the rate of surgical site infection, prevent the emergence of multidrug resistance and reduce the economic burden of treatment.

  10. AlBackr H, Alhabib KF, Sulaiman K, Jamee A, Sobhy M, Benkhedda S, et al.
    Curr Vasc Pharmacol, 2023;21(4):257-267.
    PMID: 37231723 DOI: 10.2174/1570161121666230525111259
    INTRODUCTION: PEACE MENA (Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa) is a prospective registry in Arab countries for in-patients with acute myocardial infarction (AMI) or acute heart failure (AHF). Here, we report the baseline characteristics and outcomes of in-patients with AHF who were enrolled during the first 14 months of the recruitment phase.

    METHODS: A prospective, multi-centre, multi-country study including patients hospitalized with AHF was conducted. Clinical characteristics, echocardiogram, BNP (B-type natriuretic peptide), socioeconomic status, management, 1-month, and 1-year outcomes are reported.

    RESULTS: Between April 2019 and June 2020, a total of 1258 adults with AHF from 16 Arab countries were recruited. Their mean age was 63.3 (±15) years, 56.8% were men, 65% had monthly income ≤US$ 500, and 56% had limited education. Furthermore, 55% had diabetes mellitus, 67% had hypertension; 55% had HFrEF (heart failure with reduced ejection fraction), and 19% had HFpEF (heart failure with preserved ejection fraction). At 1 year, 3.6% had a heart failure-related device (0-22%) and 7.3% used an angiotensin receptor neprilysin inhibitor (0-43%). Mortality was 4.4% per 1 month and 11.77% per 1-year post-discharge. Compared with higher-income patients, lower-income patients had a higher 1-year total heart failure hospitalization rate (45.6 vs 29.9%, p=0.001), and the 1-year mortality difference was not statistically significant (13.2 vs 8.8%, p=0.059).

    CONCLUSION: Most of the patients with AHF in Arab countries had a high burden of cardiac risk factors, low income, and low education status with great heterogeneity in key performance indicators of AHF management among Arab countries.

  11. Al Saleh A, Jamee A, Sulaiman K, Sobhy M, Gamra H, Alkindi F, et al.
    PLoS One, 2024;19(1):e0296056.
    PMID: 38206951 DOI: 10.1371/journal.pone.0296056
    BACKGROUND: The Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa (PEACE MENA) is a prospective registry program in Arabian countries that involves in patients with acute myocardial infarction (AMI) or acute heart failure (AHF).

    METHODS: This prospective, multi-center, multi-country study is the first report of the baseline characteristics and outcomes of inpatients with AMI who were enrolled during the first 14-month recruitment phase. We report the clinical characteristics, socioeconomic, educational levels, and management, in-hospital, one month and one-year outcomes.

    RESULTS: Between April 2019 and June 2020, 1377 patients with AMI were enrolled (79.1% males) from 16 Arabian countries. The mean age (± SD) was 58 ± 12 years. Almost half of the population had a net income < $500/month, and 40% had limited education. Nearly half of the cohort had a history of diabetes mellitus, hypertension, or hypercholesterolemia; 53% had STEMI, and almost half (49.7%) underwent a primary percutaneous intervention (PCI) (lowest 4.5% and highest 100%). Thrombolytics were used by 36.2%. (Lowest 6.45% and highest (90.9%). No reperfusion occurred in 13.8% of patients (lowest was 0% and highest 72.7%).Primary PCI was performed less frequently in the lower income group vs. high income group (26.3% vs. 54.7%; P<0.001). Recurrent ischemia occurred more frequently in the low-income group (10.9% vs. 7%; P = 0.018). Re-admission occurred in 9% at 1 month and 30% at 1 year, whereas 1-month mortality was 0.7% and 1-year mortality 4.7%.

    CONCLUSION: In the MENA region, patients with AMI present at a young age and have a high burden of cardiac risk factors. Most of the patients in the registry have a low income and low educational status. There is heterogeneity among key performance indicators of AMI management among various Arabian countries.

  12. Wilkie H, Das M, Pelovitz T, Bainter W, Woods B, Alasharee M, et al.
    J Allergy Clin Immunol, 2024 Jul;154(1):143-156.
    PMID: 38185418 DOI: 10.1016/j.jaci.2023.12.020
    BACKGROUND: Dedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD).

    OBJECTIVE: We sought to understand the mechanisms of eczema in DOCK8 deficiency.

    METHODS: Skin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression. Skin barrier function was measured by transepidermal water loss. Allergic skin inflammation was elicited in mice by epicutaneous sensitization with ovalbumin (OVA) or cutaneous application of Staphylococcus aureus.

    RESULTS: Skin lesions of DOCK8-deficient patients exhibited type 2 inflammation, and the patients' skin was colonized by Saureus, as in AD. Unlike in AD, DOCK8-deficient patients had a reduced FOXP3:CD4 ratio in their skin lesions, and their skin barrier function was intrinsically intact. Dock8-/- mice exhibited reduced numbers of cutaneous T regulatory (Treg) cells and a normal skin barrier. Dock8-/- and mice with an inducible Dock8 deletion in Treg cells exhibited increased allergic skin inflammation after epicutaneous sensitization with OVA. DOCK8 was shown to be important for Treg cell stability at sites of allergic inflammation and for the generation, survival, and suppressive activity of inducible Treg cells. Adoptive transfer of wild-type, but not DOCK8-deficient, OVA-specific, inducible Treg cells suppressed allergic inflammation in OVA-sensitized skin of Dock8-/- mice. These mice developed severe allergic skin inflammation and elevated serum IgE levels after topical exposure to Saureus. Both were attenuated after adoptive transfer of WT but not DOCK8-deficient Treg cells.

    CONCLUSION: Treg cell dysfunction increases susceptibility to allergic skin inflammation in DOCK8 deficiency and synergizes with cutaneous exposure to Saureus to drive eczema in DOCK8 deficiency.

  13. Jiao JY, Abdugheni R, Zhang DF, Ahmed I, Ali M, Chuvochina M, et al.
    Natl Sci Rev, 2024 Jul;11(7):nwae168.
    PMID: 39071100 DOI: 10.1093/nsr/nwae168
    Prokaryotes are ubiquitous in the biosphere, important for human health and drive diverse biological and environmental processes. Systematics of prokaryotes, whose origins can be traced to the discovery of microorganisms in the 17th century, has transitioned from a phenotype-based classification to a more comprehensive polyphasic taxonomy and eventually to the current genome-based taxonomic approach. This transition aligns with a foundational shift from studies focused on phenotypic traits that have limited comparative value to those using genome sequences. In this context, Bergey's Manual of Systematics of Archaea and Bacteria (BMSAB) and Bergey's International Society for Microbial Systematics (BISMiS) play a pivotal role in guiding prokaryotic systematics. This review focuses on the historical development of prokaryotic systematics with a focus on the roles of BMSAB and BISMiS. We also explore significant contributions and achievements by microbiologists, highlight the latest progress in the field and anticipate challenges and opportunities within prokaryotic systematics. Additionally, we outline five focal points of BISMiS that are aimed at addressing these challenges. In conclusion, our collaborative effort seeks to enhance ongoing advancements in prokaryotic systematics, ensuring its continued relevance and innovative characters in the contemporary landscape of genomics and bioinformatics.
  14. Narayanan KB, Ali M, Barclay BJ, Cheng QS, D'Abronzo L, Dornetshuber-Fleiss R, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1:S89-110.
    PMID: 26106145 DOI: 10.1093/carcin/bgv032
    Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis.
  15. Prando C, Samarina A, Bustamante J, Boisson-Dupuis S, Cobat A, Picard C, et al.
    Medicine (Baltimore), 2013 Mar;92(2):109-122.
    PMID: 23429356 DOI: 10.1097/MD.0b013e31828a01f9
    Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation. Four of these 9 variants are recurrent, affecting 25 of the 30 reported kindreds, due to founder effects in specific countries. All patients are homozygous and display complete IL-12p40 deficiency. As a result, the patients lack detectable IL-12p70 and IL-12p40 and have low levels of interferon gamma (IFN-γ). The clinical features are characterized by childhood onset of bacille Calmette-Guérin (attenuated Mycobacterium bovis strain) (BCG) and Salmonella infections, with recurrences of salmonellosis (36.4%) more common than recurrences of mycobacterial disease (25%). BCG vaccination led to BCG disease in 40 of the 41 patients vaccinated (97.5%). Multiple mycobacterial infections were rare, observed in only 3 patients, whereas the association of salmonellosis and mycobacteriosis was observed in 9 patients. A few other infections were diagnosed, including chronic mucocutaneous candidiasis (n = 3), nocardiosis (n = 2), and klebsiellosis (n = 1). IL-12p40 deficiency has a high but incomplete clinical penetrance, with 33.3% of genetically affected relatives of index cases showing no symptoms. However, the prognosis is poor, with mortality rates of up to 28.6%. Overall, the clinical phenotype of IL-12p40 deficiency closely resembles that of interleukin 12 receptor β1 (IL-12Rβ1) deficiency. In conclusion, IL-12p40 deficiency is more common than initially thought and should be considered worldwide in patients with MSMD and other intramacrophagic infectious diseases, salmonellosis in particular.
  16. Pandit PS, Anthony SJ, Goldstein T, Olival KJ, Doyle MM, Gardner NR, et al.
    Commun Biol, 2023 Jan 10;6(1):25.
    PMID: 36627372 DOI: 10.1038/s42003-022-04364-y
  17. Pandit PS, Anthony SJ, Goldstein T, Olival KJ, Doyle MM, Gardner NR, et al.
    Commun Biol, 2022 Aug 19;5(1):844.
    PMID: 35986178 DOI: 10.1038/s42003-022-03797-9
    Host-virus associations have co-evolved under ecological and evolutionary selection pressures that shape cross-species transmission and spillover to humans. Observed virus-host associations provide relevant context for newly discovered wildlife viruses to assess knowledge gaps in host-range and estimate pathways for potential human infection. Using models to predict virus-host networks, we predicted the likelihood of humans as hosts for 513 newly discovered viruses detected by large-scale wildlife surveillance at high-risk animal-human interfaces in Africa, Asia, and Latin America. Predictions indicated that novel coronaviruses are likely to infect a greater number of host species than viruses from other families. Our models further characterize novel viruses through prioritization scores and directly inform surveillance targets to identify host ranges for newly discovered viruses.
  18. Pereda J, Niimi G, Kaul JM, Mishra S, Pangtey B, Peri D, et al.
    Surg Radiol Anat, 2009 Sep;31 Suppl 1:49-93.
    PMID: 27392491 DOI: 10.1007/BF03371485
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