Peptide-based LDH5 inhibitors enter cancer cells and impair proliferation.

Lactate dehydrogenase 5 (LDH5) is overexpressed in many cancers and is a potential target for anticancer therapy due to its role in aerobic glycolysis. Small-molecule drugs have been developed as competitive inhibitors to bind substrate/cofactor sites of LDH5, but none reached the clinic to date. Recently, we designed the first LDH5 non-competitive inhibitor, cGmC9, a peptide that inhibits protein-protein interactions required for LDH5 enzymatic activity. Peptides are gaining a large interest as anticancer agents to modulate intracellular protein-protein interactions not targetable by small molecules; however, delivery of these peptides to the cytosol, where LDH5 and other anticancer targets are located, remains a challenge for this class of therapeutics. In this study, we focused on the cellular internalisation of cGmC9 to achieve LDH5 inhibition in the cytosol. We designed cGmC9 analogues and compared them for LDH5 inhibition, cellular uptake, toxicity, and antiproliferation against a panel of cancer cell lines. The lead analogue, [R/r]cGmC9, specifically impairs proliferation of cancer cell lines with high glycolytic profiles. Proteomics analysis showed expected metabolic changes in response to decreased glycolysis. This is the first report of a peptide-based LDH5 inhibitor able to modulate cancer metabolism and kill cancer cells that are glycolytic. The current study demonstrates the potential of using peptides as inhibitors of intracellular protein-protein interactions relevant for cancer pathways and shows that active peptides can be rationally designed to improve their cell permeation.

PD-L1 overexpression conveys tolerance of mesenchymal stem cell-derived cardiomyocyte-like cells in an allogeneic mouse model.

Although the autologously transplanted cells are immunologically durable, allogeneic cell transplantation is inevitable in a series of cases. Mesenchymal stem cells (MSCs) are one of the suitable candidates for cardiac tissue regeneration that have been shown to acquire immunogenicity concurrent with cardiomyogenic differentiation. The present study aimed to exploit PD-L1, as a key immunomodulatory checkpoint ligand to protect the MSCs-derived cardiomyocyte-like cells (CLCs) against the detrimental alloimmunity. Mouse bone marrow-derived MSCs were stably transduced to overexpress PD-L1. MSCs were in vitro differentiated into CLCs and the expressions of immunologic molecules were compared between MSCs and CLCs. The in vitro and in vivo allogeneic immune responses were also examined. The differentiated CLCs had higher expressions of MHC-I and CD80. Upon in vitro coculture with allogeneic splenocytes, CLCs caused more CD4+ and CD8+ T cell activation, lymphocyte proliferation, and interferon-γ (IFN-γ) release in comparison to MSCs. PD-L1 overexpression on CLCs decreased the activation of CD8+ T cells, proliferation of lymphocytes, and release of IFN-γ. The PD-L1-overexpressing CLCs elicited lower in vivo CD4+ and CD8+ T cell activation and reduced the anti-donor antibody response accompanied by increased durability and reduced T cell infiltration. The present study verified the potential of PD-L1 overexpression as a preparative strategy for the protection of allogeneic MSCs-derived CLCs against the detrimental alloreaction.

Understanding how geographic, demographic and treatment history impact health outcomes of patients with multi-drug-resistant tuberculosis in Pakistan, 2014-2017.

Tuberculosis (TB) is one of the top 10 leading causes of morbidity and mortality worldwide [1]. In 2017, approximately 10 million people were infected with TB and 1.3 million patients faced mortality [1]. Patients with active TB can infect up to 10-15 people over a year. There is a greater risk of transmission in overcrowded areas with limited air ventilation including large family units, prisons and slums [1, 2]. Without proper diagnosis and treatment, roughly 45% of non-HIV positive TB patients face mortality [1]. With the help of global organizations and national TB treatment and control programmes, the global incidence of TB is declining by approximately 2% each year [1]. The World Health Organization (WHO) TB-strategy aims to end the TB epidemic and encourages partners to fund national TB programmes to improve diagnosis and treatment of TB. The goal is to ultimately decrease death rates by 90% and decrease incidence rates by 80% [1]. To achieve these goals, the decline in TB incidence needs to reach approximately 4-5% per year [1]. The WHO 2018 TB report identified multidrug resistant TB (MDR-TB) as the leading factor hindering that goal [1]. The incidence and spread of MDR-TB has drastically increased, where approximately 558 000 new cases of MDR-TB were diagnosed in 2017 causing more than 230 000 deaths globally [1]. MDR-TB is identified by resistance to the two most powerful anti-TB treatment drugs including isoniazid and rifampicin [3]. Patients with MDR-TB are required to start second-line anti-TB drugs (SLDs), which are limited, expensive, less effective and more toxic [1,2]. Therapy duration is one of the major limitations of second-line treatments, which may require up to two years of consistent use. Since TB affects mostly developing countries, long treatment durations and associated costs become a major challenge. In 2015, 15% of new TB cases were reported as MDR-TB, which drastically increased to 24% by 2017 [1]. Even with significant improvements in molecular tests and diagnostic methods, MDR-TB is still on the rise where the success rate of treatments is between 50 and 60% [1]. Additional characteristics including socioeconomic and sociocultural factors need to be considered when targeting and treating patients with MDR-TB.

A cultural adaptation and validation of a child eating behaviour measure in a low- and middle-income country.

OBJECTIVE: The Child Eating Behaviour Questionnaire (CEBQ), a widely used instrument that has been validated mostly in high-income countries, has limitations in its factorial validity when used among different cultures. This study examines whether the CEBQ instrument is culturally appropriate and valid to be used in a low- and middle-income country (LMIC) in a setting where child undernutrition remains prevalent. DESIGN: The study employed a qualitative process to validate the content of items relative to the culture and setting, which was followed by a survey to test the psychometric properties of the instrument. Tests of factorial validity, convergent validity and reliability were performed. SETTING: Three different socio-economic settings of Yogyakarta, Indonesia. PARTICIPANTS: The participants of this study were mothers of children aged 25-60 months. In-depth interviews were conducted with twenty-four mothers and the questionnaire validation process involved 238 mothers in the survey. RESULTS: A Confirmatory Factor Analysis model with eight subscales provided the best fit (root-mean-square error of approximation = 0·048 (90 % CI 0·040, 0·057); Comparative Fit Index = 0·95 and Tucker Lewis Index = 0·95) after three new items and eight items from the original CEBQ were removed. Convergent validity with child's weight was found for two subscales, slowness in eating and satiety responsiveness. Reliability measured using Cronbach's alpha provided values between 0·62 and 0·78. CONCLUSION: The original eight-factor structure of the CEBQ showed adequate content validity and provided factorial, discriminant and convergent validity with mothers of preschool children living in a LMIC where child nutrition remains a significant public health issue.

Continuous Langmuir-Blodgett Deposition and Transfer by Controlled Edge-to-Edge Assembly of Floating 2D Materials.

The Langmuir-Blodgett technique is one of the most controlled methods to deposit monomolecular layers of floating or surface active materials but has lacked the ability to coat truly large-area substrates. In this work, by manipulating single-layer dispersions of graphene oxide (GO) and thermally exfoliated GO into water-immiscible spreading solvents, unlike traditional Langmuir-Blodgett deposition which requires densification achieved by compressing barriers, we demonstrate the ability to control the 2D aggregation and densification behavior of these floating materials using a barrier-free method. This is done by controlling the edge-to-edge interactions through modified subphase conditions and by utilizing the distance-dependent spreading pressure of the deposition solvent. These phenomena allow substrates to be coated by continuous deposition and substrate withdrawal-enabling roll-to-roll deposition and patterning of large-area substrates such as flexible polyethylene terephthalate. The aggregation and solvent-driven densification phenomena are examined by in situ Brewster angle video microscopy and by measuring the local spreading pressure induced by the spreading solvent acting on the floating materials using a Langmuir-Adam balance. As an example, the performance of films deposited in this way is assessed as passivation layers for Ag nanowire-based transparent conductors.

Fine Tuning of Antibiotic Activity by a Tailoring Hydroxylase in a Trans-AT Polyketide Synthase Pathway.

The addition or removal of hydroxy groups modulates the activity of many pharmacologically active biomolecules. It can be integral to the basic biosynthetic factory or result from associated tailoring steps. For the anti-MRSA antibiotic mupirocin, removal of a C8-hydroxy group late in the biosynthetic pathway gives the active pseudomonic acid A. An extra hydroxylation, at C4, occurs in the related but more potent antibiotic thiomarinol A. We report here in vivo and in vitro studies that show that the putative non-haem-iron(II)/α-ketoglutaratedependent dioxygenase TmuB, from the thiomarinol cluster, 4-hydroxylates various pseudomonic acids whereas C8-OH, and other substituents around the tetrahydropyran ring, block enzyme action but not substrate binding. Molecular modelling suggested a basis for selectivity, but mutation studies had a limited ability to rationally modify TmuB substrate specificity. 4-Hydroxylation had opposite effects on the potency of mupirocin and thiomarinol. Thus, TmuB can be added to the toolbox of polyketide tailoring technologies for the in vivo generation of new antibiotics in the future.

Communication: Self-assembly of a model supramolecular polymer studied by replica exchange with solute tempering.

Conventional molecular-dynamics (cMD) simulation has a well-known limitation in accessible time and length scales, and thus various enhanced sampling techniques have been proposed to alleviate the problem. In this paper, we explore the utility of replica exchange with solute tempering (REST) (i.e., a variant of Hamiltonian replica exchange methods) to simulate the self-assembly of a supramolecular polymer in explicit solvent and compare the performance with temperature-based replica exchange MD (T-REMD) as well as cMD. As a test system, we consider a relatively simple all-atom model of supramolecular polymerization (namely, benzene-1,3,5-tricarboxamides in methylcyclohexane solvent). Our results show that both REST and T-REMD are able to predict highly ordered polymer structures with helical H-bonding patterns, in contrast to cMD which completely fails to obtain such a structure for the present model. At the same time, we have also experienced some technical challenge (i.e., aggregation-dispersion transition and the resulting bottleneck for replica traversal), which is illustrated numerically. Since the computational cost of REST scales more moderately than T-REMD, we expect that REST will be useful for studying the self-assembly of larger systems in solution with enhanced rearrangement of monomers.

Binary functionalization of H:Si(111) surfaces by alkyl monolayers with different linker atoms enhances monolayer stability and packing.

Alkyl monolayer modified Si forms a class of inorganic-organic hybrid materials with applications across many technologies such as thin-films, fuel/solar-cells and biosensors. Previous studies have shown that the linker atom, through which the monolayer binds to the Si substrate, and any tail group in the alkyl chain, can tune the monolayer stability and electronic properties. In this paper we study the H:Si(111) surface functionalized with binary SAMs: these are composed of alkyl chains that are linked to the surface by two different linker groups. Aiming to enhance SAM stability and increase coverage over singly functionalized Si, we examine with density functional theory simulations that incorporate vdW interactions, a range of linker groups which we denote as -X-(alkyl) with X = CH2, O(H), S(H) or NH(2) (alkyl = C6 and C12 chains). We show how the stability of the SAM can be enhanced by adsorbing alkyl chains with two different linkers, e.g. Si-[C, NH]-alkyl, through which the adsorption energy is increased compared to functionalization with the individual -X-alkyl chains. Our results show that it is possible to improve stability and optimum coverage of alkyl functionalized SAMs linked through a direct Si-C bond by incorporating alkyl chains linked to Si through a different linker group, while preserving the interface electronic structure that determines key electronic properties. This is important since any enhancement in stability and coverage to give more densely packed monolayers will result in fewer defects. We also show that the work function can be tuned within the interval of 3.65-4.94 eV (4.55 eV for bare H:Si(111)).

The investigation of the skin biophysical measurements focusing on daily activities, skin care habits, and gender differences.

BACKGROUND: Skin, as a protective barrier to exogenous substances, can be modulated by various internal and external factors that can affect its functional state. In order to prevent the early symptoms and signs of diseases of the skin, frequent skin health assessment should be performed. The aims of the study were to evaluate four skin properties of transepidermal water loss (TEWL), hydration, elasticity, and pigmentation using a non-invasive skin assessment tool, DermaLab Combo(®) , and also to determine possible factors that may influence skin condition. METHODS: DermaLab(®) Combo was used to measure TEWL, hydration, pigmentation, and elasticity on the forearm of volunteers by using different probes. In this study, four parameters were observed to reflect the health of the skin in 100 volunteers. RESULTS: There were significant differences (P < 0.05) between TEWL, hydration, pigmentation, and elasticity in different genders on the same anatomical site of the forearm. Female subjects have a higher average value of TEWL, hydration, and elasticity compared to male subjects. The differences may be due to an individual's daily activity and use of skin care products as well as environmental factors. The use of moisturiser and drinking lots of water may keep the skin hydrated and delay the process of skin ageing as shown by the better hydration and elasticity observed (P < 0.05). CONCLUSION: In this study, it can be concluded that DermaLab(®) Combo is a reliable skin analysis instrument that offers high precision, accuracy, and reproducibility for all the measuring parameters. It has also been found that daily activities and habits influence skin condition as reflected by the measurement of these biophysical skin parameters.

Quantitative real-time polymerase chain reaction as an efficient molecular tool for detecting minimal residual disease in Moroccan chronic myeloid leukemia patients.

Chronic myeloid leukemia (CML) is characterized by BCR-ABL translocation and an increased number and migration of immature myeloid cells into the peripheral blood. The detection limit of the BCR-ABL transcript, particularly after treatment, is controversial. In the present study, we used quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) to monitor BCR-ABL expression in Moroccan CML patients undergoing imatinib treatment, and compared the results with those of conventional PCR and fluorescence in situ hybridization (FISH). The aim of this study was to establish a new molecular tool for in vitro diagnosis of CML. In a retrospective comparative analysis, 20 CML Moroccan patients who had received imatinib treatment (N = 20) were analyzed by real-time PCR, conventional RT-PCR, and FISH. Half of the samples analyzed (N = 10) were positive for BCR-ABL gene expression, while the other half (N = 10) were negative according to conventional PCR. Interestingly, 5 of the 10 samples shown to be negative by conventional PCR showed positive expression of the BCR-ABL gene according to RT-qPCR. The RT-qPCR results were confirmed by FISH, which revealed a high concordance (100%) rate. We found that real-time RT-qPCR is more reliable and should be used in Moroccan biomedical analysis laboratories to monitor CML progression, particularly for minimal residual disease, following imatinib treatment.

Density functional theory with van der waals corrections study of the adsorption of alkyl, alkylthiol, alkoxyl, and amino-alkyl chains on the H:Si(111) surface.

Surface modification of silicon with organic monolayers tethered to the surface by different linkers is an important process in realizing future miniaturized electronic and sensor devices. Understanding the roles played by the nature of the linking group and the chain length on the adsorption structures and stabilities of these assemblies is vital to advance this technology. This paper presents a density functional theory (DFT) study of the hydrogen passivated Si(111) surface modified with alkyl chains of the general formula H:Si-(CH2)n-CH2 and H:Si-X-(CH2)n-CH3, where X = NH, O, S and n = (0, 1, 3, 5, 7, 9, 11), at half coverage. For (X)-hexane and (X)-dodecane functionalization, we also examined various coverages up to full monolayer grafting in order to validate the result of half covered surface and the linker effect on the coverage. We find that it is necessary to take into account the van der Waals interaction between the alkyl chains. The strongest binding is for the oxygen linker, followed by S, N, and C, irrespective of chain length. The result revealed that the sequence of the stability is independent of coverage; however, linkers other than carbon can shift the optimum coverage considerably and allow further packing density. For all linkers apart from sulfur, structural properties, in particular, surface-linker-chain angles, saturate to a single value once n > 3. For sulfur, we identify three regimes, namely, n = 0-3, n = 5-7, and n = 9-11, each with its own characteristic adsorption structures. Where possible, our computational results are shown to be consistent with the available experimental data and show how the fundamental structural properties of modified Si surfaces can be controlled by the choice of linking group and chain length.

Electrostatic potentials of atomic nanostructures at metal surfaces quantified by scanning quantum dot microscopy.

The discrete and charge-separated nature of matter - electrons and nuclei - results in local electrostatic fields that are ubiquitous in nanoscale structures and relevant in catalysis, nanoelectronics and quantum nanoscience. Surface-averaging techniques provide only limited experimental access to these potentials, which are determined by the shape, material, and environment of the nanostructure. Here, we image the potential over adatoms, chains, and clusters of Ag and Au atoms assembled on Ag(111) and quantify their surface dipole moments. By focusing on the total charge density, these data establish a benchmark for theory. Our density functional theory calculations show a very good agreement with experiment and allow a deeper analysis of the dipole formation mechanisms, their dependence on fundamental atomic properties and on the shape of the nanostructures. We formulate an intuitive picture of the basic mechanisms behind dipole formation, allowing better design choices for future nanoscale systems such as single-atom catalysts.

Study to Determine the Prevalence of Menstrual Migraine in Reproductive-Age Women in Saudi Arabia.

BACKGROUND: Migraine is a common health condition in both men and women. Premenstrual syndrome (PMS) affects many women during their menstrual cycle, with around 50-60% of women with migraine attacks experiencing menstrual headaches. Most have mild symptoms, but 5-8% suffer from moderate to severe symptoms, causing distress and functional issues. Pure menstrual migraine (PMM) occurs in about 50% of women with migraine, and it can be debilitating in terms of frequency and severity. This information is crucial for Saudi Arabian medical professionals to provide better care and support, improving the quality of life for women with PMS and menstrual migraine (MM) attacks. OBJECTIVES: To estimate the prevalence of MM in women, to evaluate the severity and frequency of MM in women with PMS, and to identify potential risk factors aggravating MM in women with PMS in Saudi Arabia. METHODOLOGY: A cross-sectional community-based study was conducted on reproductive-aged (18-50 years) women who had regular menstrual cycles and were diagnosed with PMS, using a self-administered questionnaire between December 2022 to May 2023 in Saudi Arabia. RESULTS: Out of the 2130 female participants, 397 (18.6%) had migraine. Among these 397 migraine sufferers, 230 (57.9%) experienced MM, while 167 (42.1%) had non-MM. In reproductive women in general, MM occurred in 10.7% of cases, while non-MM was observed in 7.8%. There is a correlation between increasing BMI and an increased incidence of MM. About one-third of the participants experienced moderate disability due to migraine attacks, with 134 (33.8%) individuals affected. Additionally, most MM sufferers missed at least 3 days of work in the last 3 months due to their condition. CONCLUSIONS: Migraine attacks occurring during the menstrual cycle impair the ability to engage in social, physical, household, and academic activities, often hindering the fulfillment of professional commitments. To gain a deeper understanding of menstrual and non-menstrual migraine attacks, it is essential to conduct extensive prospective studies aimed at developing effective management strategies.

Management of bilateral congenital choanal atresia.

This study was conducted to adopt better management technique for better outcome of bilateral congenital choanal atresia. Six consecutive neonates with bilateral congenital choanal atresia were included in this study. Emergency and elective management was done in various ways. Postoperative outcome was assessed clinically and endoscopically. Surgical management was done in two approaches. Three done in endoscopic transnasal approach and another 3 in transpalatine approach. Patient with endoscopic approach recovered earlier with minimum morbidity. Application of mitomycin-c minimizes granulation tissue and adhesions. Management of bilateral congenital choanal atresia is better by endoscopic transnasal approach with application of mitomycin-c.

A 9 years boy with MEN-2B variant of medullary thyroid carcinoma.

To highlight a rare disease like multiple endocrine neoplasia (MEN)-2B variant of medullary thyroid carcinoma and to optimize the management option in such cases, we present a nine year old boy with thyroid swelling, cervical lymphadenopathy and thick lips. His calcitonin level was raised. Investigation's results of the boy were as following fine needle aspiration cytology (FNAC) was medullary carcinoma of thyroid, preoperative calcitonin was >2000pg/ml, post operative histopathological report was medullary carcinoma. Total thyroidectomy with aggressive initial neck surgery may reduce the recurrence and increase better prognosis and survival rate. Calcitonin is used as diagnostic and follow-up marker.

Estimation of the contribution of private providers in tuberculosis case notification and treatment outcome in Pakistan.

To improve involvement of the private sector in the national tuberculosis (TB) programme in Pakistan various public-private mix projects were set up between 2004 and 2009. A retrospective analysis of data was made to study 6 different public-private mix models for TB control in Pakistan and estimate the contribution of the various private providers to TB case notification and treatment outcome. The number of TB cases notified through the private sector increased significantly from 77 cases in 2004 to 37,656 in 2009. Among the models, the nongovernmental organization model made the greatest contribution to case notification (58.3%), followed by the hospital-based model (18.9%). Treatment success was highest for the district-led model (94.1%) and lowest for the hospital-based model (74.2%). The private sector made an important contribution to the national data through the various public-private mix projects. Issues of sustainability and the lack of treatment supporters are discussed as reasons for lack of success of some projects.

Wastewater-based epidemiology for tracking bacterial diversity and antibiotic resistance in COVID-19 isolation hospitals in Qatar.

BACKGROUND: Hospitals are hotspots for antimicrobial resistance genes (ARGs), and play a significant role in their emergence and spread. Large numbers of ARGs will be ejected from hospitals via wastewater systems. Wastewater-based epidemiology has been consolidated as a tool to provide real-time information, and represents a promising approach to understanding the prevalence of bacteria and ARGs at community level. AIMS: To determine bacterial diversity and identify ARG profiles in hospital wastewater pathogens obtained from coronavirus disease 2019 (COVID-19) isolation hospitals compared with non-COVID-19 facilities during the pandemic. METHODS: Wastewater samples were obtained from four hospitals: three assigned to patients with COVID-19 patients and one assigned to non-COVID-19 patients. A microbial DNA quantitative polymerase chain reaction was used to determine bacterial diversity and ARGs. FINDINGS: The assay recorded 27 different bacterial species in the samples, belonging to the following phyla: Firmicutes (44.4%), Proteobacteria (33.3%), Actinobacteria (11%), Bacteroidetes (7.4%) and Verrucomicrobiota (3.7%). In addition, 61 ARGs were detected in total. The highest number of ARGs was observed for the Hazem Mebaireek General Hospital (HMGH) COVID-19 patient site (88.5%), and the lowest number of ARGs was found for the HMGH non-patient site (24.1%). CONCLUSION: The emergence of contaminants in sewage water, such as ARGs and high pathogen levels, poses a potential risk to public health and the aquatic ecosystem.

Accurate quantification of the stability of the perylene-tetracarboxylic dianhydride on Au(111) molecule-surface interface.

Studying inorganic/organic hybrid systems is a stepping stone towards the design of increasingly complex interfaces. A predictive understanding requires robust experimental and theoretical tools to foster trust in the obtained results. The adsorption energy is particularly challenging in this respect, since experimental methods are scarce and the results have large uncertainties even for the most widely studied systems. Here we combine temperature-programmed desorption (TPD), single-molecule atomic force microscopy (AFM), and nonlocal density-functional theory (DFT) calculations, to accurately characterize the stability of a widely studied interface consisting of perylene-tetracarboxylic dianhydride (PTCDA) molecules on Au(111). This network of methods lets us firmly establish the adsorption energy of PTCDA/Au(111) via TPD (1.74 ± 0.10 eV) and single-molecule AFM (2.00 ± 0.25 eV) experiments which agree within error bars, exemplifying how implicit replicability in a research design can benefit the investigation of complex materials properties.

Identification and characterization of aldehyde dehydrogenase (ALDH) gene superfamily in garlic and expression profiling in response to drought, salinity, and ABA.

In response to biotic and abiotic stressors, aldehydes are detoxified and converted to carboxylic acids by aldehyde dehydrogenases (ALDHs), which are enzymes that use NAD+/NADP+ as cofactors. Garlic (Allium sativum L.) has not yet undergone a systematic examination of the ALDH superfamily, despite the genome sequence having been made public. In this investigation, we identified, characterized, and profiled the expression of the garlic ALDH gene family over the entire genome. The ALDH Gene Nomenclature Committee (AGNC) classification was used to classify and name the 34 ALDH genes that were discovered. Except for chromosome 8, all AsALDH genes were dispersed across the chromosomes. AsALDH genes have various localizations, according to predictions about subcellular localization. The AsALDH proteins are more varied and closely related to rice than to Arabidopsis, according to a study of conserved motifs and phylogenetic relationships. The presence of stress modulation pathways is indicated by the abundance of stress-related cis-elements in the AsALDH genes' promoter regions. Analysis of the RNA-seq data showed that AsALDHs expressed differently in various tissues and at various developmental stages. Nine AsALDHs were chosen for study using RT-qPCR, and the results revealed that the majority of the genes were upregulated in response to ABA and downregulated in response to salinity and drought. The results of this study improved our knowledge of the traits, evolutionary background, and biological functions of AsALDHs genes in growth and development.

Study to determine the epidemiology of treatment-resistant depression among the Saudi Arabian population: A cross-sectional study.

BACKGROUND: Depression is a common mental health disorder that affects millions of people worldwide. Globally, major depressive disorder (MDD) is a public health concern; nearly, it affects more than 300 million people. The coronavirus disease 2019 (COVID-19) pandemic lockdown, travel restrictions, social distancing, and COVID-19 vaccine acceptance have aggravated psychological disorders, such as depression and suicidal tendencies. Treatment-resistant depression (TRD) is typically defined as a lack of response to at least two different antidepressant medications or psychotherapies. TRD is common and has been associated with higher comorbidities and prolonged duration of illness, leading to a substantial medical and economic burden. MATERIALS AND METHODS: A cross-sectional study was designed to determine the epidemiology and estimate the prevalence of TRD in Abha City, Assir Region, Kingdom of Saudi Arabia. The study includes adult patients who were attended to the psychiatry department and aged 18-65 years diagnosed with major depressive depression. A total of 651 study participants were recruited. RESULTS: Of the total 651 depressive disorder cases, 134 (20.6%) were reported as TRD and the remaining 517 (79.4%) were nontreatment-resistant depressive cases. Of the 651 depression participants, 176 (27%) were males and 475 (73%) were females. More than one-quarter (180 (28%)) had been associated with chronic morbidity. One-tenth of the depressive patients were suffering from thyroid disorders, followed by hypertension (10%), autoimmune diseases (10%), and diabetes mellitus (8%). CONCLUSIONS: TRD emerged as a threat to public health and challenging psychiatric care providers, and further innovative techniques and effective newer drugs to treat depression need to be researched. The treatment complaint mechanism is warranted, encouraging people to get treatment from the psychiatrist by removing the stigma of mental illness, which is needed to improve the quality of life of TRD patients.