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Alif Noeriyanto Rahman,1,2 Herry Herman,2,3 Eri Kriswanto,2,4 Ahmad Faried,2,5 Mochammad Kamal Nasser6 1Musculoskeletal Pain Intervention and Regeneration, Faculty of Medicine Universitas Padjadjaran, Orthopaedic and Pain Intervention Center of Sentra Medika Hospital, Depok, Indonesia; 2Pain Intervention and Regeneration, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 3Department of Orthopaedic and Traumatology Hasan Sadikin General Hospital Faculty of Medicine Padjadjaran University, Bandung, West Java, Indonesia; 4Department of Orthopaedic and Traumatology Baptist Hospital, Kediri, Indonesia; 5Department of Neurosurgery, Hasan Sadikin General Hospital Faculty of Medicine Padjadjaran University, Bandung, West Java, Indonesia; 6Baptist Hospital, Kediri, IndonesiaCorrespondence: Alif Noeriyanto Rahman, Musculoskeletal Pain Interventional and Regeneration, Faculty of Medicine Universitas Padjadjaran, Orthopaedic and Pain Intervention Center of Sentra Medika Hospital, RS Sentra Medika Cisalak Depok (Jl Raya Jakarta Bogor, Cisalak, Kota Depok, Jawa Barat), Depok, Indonesia, Tel +6281233889873, Email alifrahman1979@gmail.comBackground: Knee osteoarthritis (OA) is a chronic and progressive degenerative disease. It resulted from mechanical and chemical disorders that damage the joint and the underlying bone. The management of knee OA is challenging due to poor self-regeneration of connective tissues. Surgical treatment with prolotherapy approaches was conducted to treat medial compartment knee OA.Aim: To know the injection frequency to reach a 50% improvement in VAS score and WOMAC index.Methods: Six patients who suffered from late-stage medial compartment knee OA underwent PFO followed by twelve sessions of intra-articular dextrose prolotherapy. The subjective pain score, visual analog scale (VAS), was assessed based on the patient subjectiveness before and after treatment. Patients marked the score from 0 to 10 cm to describe the current pain state. The functional index, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index used to evaluate the Patient’s clinical symptoms. It ranges from 0 to 96 points consisting of three main sections: pain (total 20 points), stiffness (total: eight points), and physical function disability (total 68 points). Higher scores indicate severe symptoms and function.Results: Four patients showed pain relief and functional improvement with more than 50% scores of VAS and WOMAC after the treatment. Two patients received more than twelve doses of intra-articular dextrose prolotherapy due to a lack of progress.Conclusion: This study provides clinical evidence for a new treatment strategy for advanced knee OA. This combined therapy improves the patient’s daily activity function and postpones the need for total knee arthroplasty (TKA).Keywords: knee osteoarthritis, proximal fibula osteotomy, dextrose prolotherapy

Angliana Chouw,1,2 Cynthia Retna Sartika,2 Tiana Milanda,3 Ahmad Faried4 1Doctoral Program, Faculty of Pharmacy Universitas Padjadjaran, Jatinangor, West Java, Indonesia; 2Research and Development, Prodia StemCell Indonesia, Jakarta, DKI, Jakarta, Indonesia; 3Department of Biological Pharmacy, Faculty of Pharmacy Universitas Padjadjaran, Jatinangor, West Java, Indonesia; 4Stem Cell Working Group, Faculty of Medicine Universitas Padjadjaran, Dr. Hasan Sadikin Hospital, Bandung, West Java, IndonesiaCorrespondence: Angliana Chouw; Tiana Milanda, Email angliana@prostem.co.id; tiana.milanda@unpad.ac.idBackground: Umbilical cord mesenchymal stem cells (UC-MSCs)-derived secretome is currently used in regenerative therapy. MSCs are believed to secrete a wide spectrum of bioactive molecules which give paracrine effects in immunomodulation and regenerative capacities. One group that was found in secretome is interleukins (ILs), a cytokine that plays an essential role in the process of proliferation, differentiation, maturation, migration, and adhesion of immune cells. However, as there are many types of ILs, the profile of ILs in the UC-MSCs-derived secretome has been limitedly reported. Therefore, in this study, we would like to profile and detect the interleukin concentration secreted by UC-MSCs.Methods: UC-MSCs-derived secretome was collected from UC-MSCs passage 5 after 24- and 48-hour incubation (n=9). Secretome was filtered using 0.2 μm and stored at − 80°C for further detection. All samples were normalized before the interleukin (IL-2, IL-4, IL-6, IL-9, IL-10, IL-12, IL-17A) detection using a MACSPlex Cytokine Kit.Results: The IL-6 has the highest concentration among other interleukins in both groups and increases significantly (p< 0.003) after incubation for 48 hours. The pro-inflammatory factors are decreasing while anti-inflammatory factors are increasing after 48-hour incubation.Discussion: Our studies show that the UC-MSCs secrete pro- and anti-inflammatory interleukins. The concentration of anti-inflammatory interleukins shows to be increasing, while the pro-inflammatory interleukins are decreasing within the longer incubation time, but this not be applicable for IL-10 and IL-6. IL-6 has the highest concentration among other ILs. These results may provide important clues regarding when is the right time for secretome to be used in therapy patients, because all the molecules in the secretome can lead to many clinical manifestations.Keywords: secretome, mesenchymal stem cell, interleukin, conditioned medium, umbilical cord

Abstract Background Timely identification of people who are at risk of dying is an important first component of end-of-life care. Clinicians often fail to identify such patients, thus trigger tools have been developed to assist in this process. We aimed to evaluate the performance of a identification tool (based on the Gold Standards Framework Prognostic Indicator Guidance) to predict death at 12 months in a population of hospitalised patients in South Africa. Methods Patients admitted to the acute medical services in two public hospitals in Cape Town, South Africa were enrolled in a prospective observational study. Demographic data were collected from patients and patient notes. Patients were assessed within two days of admission by two trained clinicians who were not the primary care givers, using the identification tool. Outcome mortality data were obtained from patient folders, the hospital electronic patient management system and the Western Cape Provincial death registry which links a unique patient identification number with national death certificate records and system wide electronic records. Results 822 patients (median age of 52 years), admitted with a variety of medical conditions were assessed during their admission. 22% of the cohort were HIV-infected. 218 patients were identified using the screening tool as being in the last year of their lives. Mortality in this group was 56% at 12 months, compared with 7% for those not meeting any criteria. The specific indicator component of the tool performed best in predicting death in both HIV-infected and HIV-uninfected patients, with a sensitivity of 74% (68–81%), specificity of 85% (83–88%), a positive predictive value of 56% (49–63%) and a negative predictive value of 93% (91–95%). The hazard ratio of 12-month mortality for those identified vs not was 11.52 (7.87–16.9, p

Secara geografis, meskipun letak Indonesia memiliki potensi sumber daya alam yang luar biasa, tapi juga rawan terhadap potensi bencana alam, terutama bencana tanah longsor. Hal ini disebabkan banyakanya pegunungan dan gunung di Indonesia, termasuk Kabupaten Madiun yang memiliki Gunung Wilis. Kabupaten Madiun merupakan daerah yang terkena dampak dari bencana tanah longsor. Sehingga, paper ini bertujuan untuk menginvestigasi Kawasan Rawan Bencana (KRB) tanah longsor di Kabupaten Madiun dengan menggunakan Sistem Informasi Geografis (SIG). Penelitian ini menggunakan data sekunder yang bersumber dari SRTM USGS, data BMKG, Google Earth, dan data BPS Kabupaten Madiun yang diolah menggunakan software ArcGis 10.7 dengan metode Analysis Union Overlay berdasarkan pembobotan pada peta parameter bencana tanah longsor. Data yang diolah menghasilkan peta kepadatan penduduk, geologi, curah hujan, kemiringan lereng, dan peta KRB Tanah Longsor Kabupaten Madiun. Peta KRB Tanah Longsor menunjukkan bahwa Kabupaten Madiun memiliki kerawanan yang relatif rendah (aman) terhadap tanah longsor. Daerah di Kabupaten Madiun yang berpotensi mengalami tanah longsor adalah sebelah barat Kabupaten Madiun yaitu kecamatan Pilangkenceng, Balerejo, Jiwan, dan sebagain Kecamatan Kebonsari dan Dolopo dengan luas sebesar 192.07 km2 untuk kerawanan tinggi dan 1.39 km2 untuk kerawanan sangat tinggi. Hal ini karena kecamatan-kecamatan tersebut memiliki curah hujan yang ekstrem dengan intensitas diatas 150 mm dan kepadatan penduduk yang relatif padat hingga sangat padat. Peta KRB Tanah Longsor Kabupaten Madiun dapat menjadi sumber referensi bagi warga setempat dan khalayak umum untuk mengetahui titik rawan bencana tanah longsor di Kabupaten Madiun sehingga dapat mempersiapkan mitigasi bencana tanah longsor untuk meminimalisir dampak dan kerugian yang terjadi.

Objective(s): Skin aging is a degenerative process that can be induced by UV irradiation. UV radiation can produce reactive oxidate stress which causes premature aging. This study aims to examine the antiaging potential of secretome gel (SC) from human Wharton Jelly Mesenchymal Stem Cells (hWJ-MSCs) in a UVB-induced mice model. Materials and Methods: The secretome was obtained from hWJ-MSCs and made in gel form. Male mice were radiated by UVB for 15 min twice daily for 14 days. The gel was topically applied to the mice’s dorsal skin. Two treatments of secretome gel: secretome 1 is applied once and secretome 2 is applied twice daily after UVB radiation. TGF-β1, IL-10, and IL-18 gene expression was determined using RT-PCR. Hematoxylin Eosin staining was used to observe the inflammation and collagen density of skin tissue. An immunohistochemistry assay was used to analyze the protein expression of P53, COL4A1, MMP-2, and MMP-13. The data were statistically analyzed using the ANOVA test followed by the Tukey post hoc test (P

Head trauma is a head injury caused by external forces in the head or body that results in disruption of the normal functioning of the brain. According to the CDC, deaths from head injuries were about 60,000 in 2016, and rose to more than 61,000 in 2017. The COVID-19 pandemic had caused poor non-COVID patient care, especially in low- and lower-middle-income countries with limited access to health facilities, resulting in increased morbidity and mortality, including among patients with head injuries. The purpose of this study was to understand the characteristics, duration of hospital stay, and difference of time to surgery interval in Traumatic Brain Injury patients in Dr. Hasan Sadikin General Hospital Bandung before and during the COVID-19 pandemic. This study was performed through analytical methods with a cross-sectional study design using analysis of medical records of head trauma patients treated in Dr. Hasan Sadikin General Hospital Bandung, Indonesia in the period before the pandemic (February 2018-February 2020) and during the pandemic (March 2020 - September 2021). Data analysis showed significant differences in length of hospitalization and operating intervals before and during the pandemic (p=0.04 and p=0.03), showing that there are differences in interval operation and duration of stay between patients with head trauma before the pandemic and during the pandemic.

Dendritic cell (DC) vaccines, as immunotherapy agents, can gather up and transport cancer-related antigens to T lymphocytes, activating anti-tumor effector responses. After being activated by DC, cytotoxic T lymphocyte cells (CTL) will secrete the cytolytic granzyme B that can effectively induce rapid apoptosis of target cells. On the other hand, DC also secrete several cytokines and a large number of exosomes, which together operate as a whole antigen-presenting entity. The efficacy of the vaccine’s treatment may be affected by the sources used for DC vaccines. Umbilical cord blood (UCB) from healthy donors can be employed when autologous cancer patient’s peripheral blood (PB) cannot be used as a source for isolating DC due to genetic abnormalities. Comparing UCB to other sources, there is a painless method of collecting sources as opposed to PB, which necessitates a venipuncture or leukapheresis procedure to isolate the blood. Many studies related to the use of PB-DC have been carried out, but research on potential comparisons between PB-DC and UCB-DC is still very limited. In this review, the potential of PB- and UCB-derived DC and their secretomes for cancer will be discussed. Keywords: dendritic cells, vaccines, umbilical cord blood, peripheral blood

Abstract Background Many individuals with substance use disorders face challenges in their social interactions and often have strained relationships with peers. Challenges related to problem-solving, stress management, and impulsivity often contribute to their substance use disorders. Emotional intelligence plays a pivotal role in assisting individuals with substance use disorders in coping with stress, enhancing peer connections, resolving problems, and preventing relapse. Consequently, our study aimed to assess emotional intelligence in individuals with substance use disorders and explore the factors influencing it. A cross-sectional study compared 50 individuals with substance use disorders and 50 healthy individuals. We assessed various factors, including clinical data, sociodemographic variables, family socioeconomic status, Addiction Severity Index (ASI) scores, and Emotional Intelligence (EI) scale scores. Results Individuals with substance use disorders had significantly lower mean scores in total EI and its subscales compared to the healthy control group. Additionally, a higher percentage of individuals with substance use disorders exhibited low EI levels, while healthy individuals demonstrated better EI. Furthermore, there was a substantial association between higher ASI scores in individuals with substance use disorders and lower EI scores. Conclusions Lower EI scores are associated with an increased risk of substance use disorders. Also, can contribute to difficulties in impulse control, and challenges in managing relationships and stress. These findings underscore EI crucial role in preventing and treating substance use disorders.

Purpose To assess the causes and management of low vision in school-age children in Menoufia Governorate. Patients and methods This prospective study was made among 140 children with vision impairment aged from 6 to 18 years who came to the low-vision clinic of the Department of Ophthalmology of Menoufia University Hospitals with visual acuity less than 6/18 in the better eye best correction. A complete history was obtained. Complete examination of the anterior and posterior segments was done. Strabismus existence was determined. Refractive errors were measured. Before and after using low-vision aids, near and far visual acuity was measured. Results The mean age of patients was 11.94±3.61 years; 76 (54.29%) of the children were males and 64 (45.71%) of the children were females. According to the distribution of the diagnoses, hereditary fundus dystrophies were the most prevalent diagnosis among the children, accounting for 28.57% of diagnoses, followed by albinism (20%). The rehabilitation techniques that were mostly used were telescopic glasses (54.29%) for distant vision, electronic magnifiers (31.43%), and optical magnifiers (20.0%) for near vision. Low-vision devices were shown to significantly improve both near and distant visual acuity. Conclusions Visual rehabilitation for school-age children with visual impairment can result in a considerable improvement in both distant and near vision. As a result, pediatricians and ophthalmologists must recommend vision rehabilitation for children with vision impairment.

BACKGROUND: Stroke is one of many leading causes of death and disability worldwide. Despite decades of research, treatment for stroke recovery is still inadequate. Recently, mesenchymal stem cell (MSC) therapy is considered as one of the potential treatments for stroke due to their capabilities to repair or regenerate damaged tissues, as well as immunomodulators in inflammatory conditions. Many pre-clinical and clinical trials have shown MSC therapy feasibility, safety, and efficacy in treating stroke. However, evidence regarding the optimal treatment plan and factors that can improve stem cell functional outcomes in treating stroke needs to be further explored. Therefore, a systematic review was conducted. METHODS: Recent literatures from 2015-2022 regarding stem cell therapies, specifically MSC on ischemic stroke, were collected from two reliable databases: PubMed and PubMed Central. Collected literatures were properly applied to inclusion-exclusion criteria and appraised critically. Keyword strategies on databases were employed, including both medical subject headings (MeSH). RESULTS: Five literatures from 726 were identified and used for systematic review. All animal model in the literatures were prepared to have middle cerebral artery occlusion. All studies indicated that MSC therapy is a safe and reliable procedure despite the variety of transplantation routes. No report of toxicity, rejection reaction, nor infection on MSC treated groups. CONCLUSION: Stem cell sources, dosages, and delivery routes could be resourceful for future translational studies to ensure the safety and efficacy of MSC therapy for ischemic stroke. KEYWORDS: ischemic stroke, mesenchymal stem cells, regenerative medicine, immunomodulator

Abstract Pakistan is the 8th most climate-affected country in the globe along with a semi-arid to arid climate, thereby the crops require higher irrigation from underground water. Moreover, ~ 70% of pumped groundwater in irrigated agriculture is brackish and a major cause of secondary salinization. Cucumber (Cucumis sativus L.) is an important vegetable crop with an annual growth rate of about 3.3% in Pakistan. However, it is a relatively salt-sensitive crop. Therefore, a dire need for an alternate environment-friendly technology like grafting for managing salinity stress in cucumber by utilizing the indigenous cucurbit landraces. In this regard, a non-perforated pot-based study was carried out in a lath house to explore indigenous cucurbit landraces; bottle gourd (Lagenaria siceraria) (cv. Faisalabad Round), pumpkin (Cucurbit pepo. L) (cv. Local Desi Special), sponge gourd (Luffa aegyptiaca) (cv. Local) and ridge gourd (Luffa acutangula) (cv. Desi Special) as rootstocks for inducing salinity tolerance in cucumber (cv. Yahla F1). Four different salts (NaCl) treatments; T0 Control (2.4 dSm–1), T1 (4 dSm–1), T2 (6 dSm–1) and T3 (8 dSm–1) were applied. The grafted cucumber plants were transplanted into the already-induced salinity pots (12-inch). Different morpho-physio-biochemical, antioxidants, ionic, and yield attributes were recorded. The results illustrate that increasing salinity negatively affected the growing cucumber plants. However, grafted cucumber plants showed higher salt tolerance relative to non-grafted ones. Indigenous bottle gourd landrace (cv. Faisalabad Round) exhibited higher salt tolerance compared to non-grafted cucumber plants due to higher up-regulation of morpho-physio-biochemical, ionic, and yield attributes that was also confirmed by principal component analysis (PCA). Shoot and root biomass, chlorophylls contents (a and b), activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POX) enzymes, antioxidants scavenging activity (ASA), ionic (↑ K and Ca, ↓ Na), and yield-related attributes were found maximum in cucumber plants grafted onto indigenous bottle gourd landrace. Hence, the indigenous bottle gourd landrace ‘cv. Faisalabad round’ may be utilized as a rootstock for cucumber under a mild pot-based saline environment. However, indigenous bottle gourd landrace ‘cv. Faisalabad round’ may further be evaluated as rootstocks in moderate saline field conditions for possible developing hybrid rootstock and, subsequently, sustainable cucumber production.

Abstract In this paper, we introduce some user-friendly versions of integral-type fixed-point results and give some modifications of the classical Banach contraction principle by constructing a special type of contractive restrictions of integral forms for weak contraction mappings defined on 1 E $1_{E}$ -complete multiplicative partial cone metric spaces over Banach algebras and formulate some existence and uniqueness results regarding the fixed-point theorems using some integrative conditions. Moreover, we validate the significance our results and exploit them to find the unique solution of a fractional nonlinear differential equation of Caputo type, which complements some previously well-known generalizations found in the literature.

Abstract Microalgae have the potential to become the primary source of biodiesel, catering to a wide range of essential applications such as transportation. This would allow for a significant reduction in dependence on conventional petroleum diesel. This study investigates the effect of biostimulation techniques utilizing nanoparticles of Magnesium oxide MgO, Calcium hydroxyapatite Ca10(PO4)6(OH)2, and Zinc oxide ZnO to enhance the biodiesel production of Chlorella sorokiniana. By enhancing cell activity, these nanoparticles have demonstrated the ability to improve oil production and subsequently increase biodiesel production. Experimentally, each nanomaterial was introduced at a concentration of 15 mg L−1. The results have shown that MgO nanoparticles yielded the highest biodiesel production, with a recorded yield of 61.5 mg L−1. Hydroxyapatite nanoparticles, on the other hand, facilitated lipid accumulation. ZnO nanoparticles showcased a multifaceted advantage by enhancing both growth and lipid content. Thus, it is suggested that these nanoparticles can be used effectively to increase the lipid content of microalgae. These findings highlight the potential of biostimulation strategies utilizing MgO, hydroxyapatite, and zinc oxide nanoparticles to bolster biodiesel production.

This investigation concentrates on refining the accuracy of earthquake parameters as reported by various Saudi seismic networks, addressing the significant challenges arising from data discrepancies in earthquake location, depth, and magnitude estimations. The application of sophisticated machine learning techniques, particularly the Isolation Forest algorithm, has markedly enhanced the precision in the estimation of seismicity parameters by effectively identifying and eliminating outliers and discrepancies. A newly developed and refined seismicity catalog was employed to accurately determine key seismic parameters such as the magnitude of completeness (Mc), a-value, and b-value, thereby underlining their indispensable role in regional seismic hazard assessment. The research underscores the substantial impact of data inconsistencies on the evaluation of seismic hazards, thereby advocating for the advancement of research methodologies within the field of seismotectonics. The insights derived from this study significantly contribute to a more profound understanding of the seismotectonic processes in the region. These insights are crucial for the development of comprehensive seismic hazard assessments and the formulation of targeted earthquake preparedness strategies, thereby enhancing resilience against seismic risks in the region.

Mohammed S Almuhayawi,1 Mohammed H Alruhaili,1,2 Hattan S Gattan,2,3 Mohanned Talal Alharbi,4 Mohammed Nagshabandi,4 Soad Al Jaouni,5,6 Samy Selim,7 Awadh Alanazi,7 Yasir Alruwaili,7 Osama Ahmed Faried,8 Mohamed E Elnosary9 1Department of Clinical Microbiology and Immunology, Faculty of Medicine, King AbdulAziz University, Jeddah, Saudi Arabia; 2Special Infectious Agents Unit, King Fahad Medical Research Center, King AbdulAziz University, Jeddah, Saudi Arabia; 3Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Medical Microbiology and Parasitology, Faculty of Medicine, University of Jeddah, Jeddah, 23218, Saudi Arabia; 5Department of Hematology/Oncology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 6Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 7Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia; 8Medical Microbiology and Immunology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt; 9Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, EgyptCorrespondence: Mohammed S Almuhayawi; Samy Selim, Email msalmuhayawi@kau.edu.sa; sabdulsalam@ju.edu.saBackground: Wound infection is a prevalent concern in the medical field, being is a multi-step process involving several biological processes. Methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) infections often occur in areas of damaged skin, such as abrasions and open wounds.Methods: This research aims to light the incidence of MRSA and VRSA in wound swabs, the antimicrobial susceptibility configuration of isolated S. aureus patterns in pus/wound samples collected from Saudi Arabian tertiary hospital. The cross section study, β- lactamase detection, VRSA genotyping, MAR index, D-test and VRSA genotyping are methods, which used for completed this research.Results: Patients of several ages and genders delivered specimens from two hospitals in the Al jouf area, in the northern province of Saudi Arabia. S. aureus was found in 188 (34.7%) of the 542 wounds. The traumatized wounds provided 71 isolates (38.8%), surgical wound provided 49 isolates (26.8%) and abscess were represented 16 by isolates (8.7%). In the study, 123 (65.4%) out of 188 were MRSA, 60 (31.9%) were MSSA, and five (2.7%) were VRSA. Linezolid and rifampin were found to be the most effective antimicrobials with 100% in vitro antibacterial activity against S. aureus isolates. The Multiple antimicrobials resistance (MAR) index revealed 73 isolates (38.9%) with a MAR index greater than 0.2, and 115 (61.1%) less than 0.2. The D-test showed that of MLSb phenotypes among S. aureus, 22 (11.7%) strains were D-test positive (MLSbi phenotype), 53 (28.2%) strains were constitutive MLSc phenotypes, and 17 (9%) strains were shown to have MSb phenotypes. All VRSA isolates (n=5) were found to be positive for vanA, and no vanB positive isolates were detected in the study.Conclusion: Regular monitoring and an antimicrobials stewardship program should be in place to provide critical information that can be utilized for empirical therapy and future prevention strategies.Keywords: methicillin, vancomycin, resistant, Staphylococcus aureus, emergence, virulent, wound infection, MAR index, D-test, tertiary hospital, Saudi Arabia

Abstract Inflammatory response in COVID-19 contributes greatly to disease severity. Mesenchymal Stem Cells (MSCs) have the potential to alleviate inflammation and reduce mortality and length of stay in COVID-19 patients. We investigated the safety and effectiveness of normoxic-allogenic umbilical cord (NA-UC)-MSCs as an adjunctive treatment in severe COVID-19 patients. A double-blind, multicentric, randomized, placebo-controlled trial involving severe COVID-19 patients was performed from January to June 2021 in three major hospitals across Java, Indonesia. Eligible participants (n = 42) were randomly assigned to two groups (1:1), namely the intervention (n = 21) and control (n = 21) groups. UC-MSCs dose was 1 × 106 /kg body weight on day D0, D3, and D6. The primary outcome was the duration of hospitalization. Meanwhile, the secondary outcomes were radiographical progression (Brixia score), respiratory and oxygenation parameters, and inflammatory markers, in addition to the safety profile of NA-UC-MSCs. NA-UC-MSCs administration did not affect the length of hospital stay of severe COVID-19 patients, nor did it improve the Brixia score or mMRC dyspnoea scale better than placebo. Nevertheless, NA-UC-MSCs led to a better recuperation in oxygenation index (120.80 ± 72.70 baseline vs. 309.63 ± 319.30 D + 22, p = 0.038) and oxygen saturation (97.24 ± 4.10% vs. 96.19 ± 3.75% in placebo, p = 0.028). Additionally, compared to the placebo group, the treatment group had a significantly smaller increase in PCT level at D + 22 (1.43 vs. 12.76, p = 0.011). No adverse effects, including serious ones, were recorded until D + 91. NA-UC-MSCs therapy is a very safe adjunct for COVID-19 patients. It improves the oxygenation profile and carries potential to suppress inflammation.

BackgroundFor over 30 years, syringe services programs (SSPs) have served as an efficacious intervention for the prevention of HIV and Hepatitis C transmission among persons who use drugs. Despite a strong body of evidence for the effectiveness of SSPs as a preventative public health measure, numerous local and state governments in the United States continue to resist the establishment of new SSPs and aggressively pursue the closure of those already in operation.CommentaryIn Orange County, California, local officials have repeatedly mobilized in opposition of the establishment of syringe access - thereby hindering access to healthcare for thousands of predominantly unhoused individuals. The county was previously served by the Orange County Needle Exchange Program from 2016 until 2018 when a civil suit brought by the Orange County Board of Supervisors resulted in the closure of the program. For more than 2 years, persons who inject drugs in Orange County lacked reliable access to clean syringes, placing them at increased risk for contracting HIV and Hepatitis C. Here, we comment on the ongoing effort to restore syringe access in Orange County. This collaborative physician-directed endeavor has brought together students and community volunteers to provide vital harm reduction services to a remarkably underserved population. Since the reestablishment of syringe access in Orange County by the Harm Reduction Institute, new legal barriers have arisen including the passage of new municipal legislation banning the operation of syringe exchanges. We are well-equipped to overcome these obstacles. This work serves as an affirmation of assertions made by previous authors regarding the unique qualifications of medical & graduate students as effective harm reductionists.ConclusionHarm reduction services are vital to the health and well-being of people who use drugs. The provision of these services should not be impeded by legislative interference by municipal, county, or state governments.