Diseases

Background: Diabetic peripheral neuropathy (DPN) is known to predict foot ulceration, lower-extremity amputation and mortality. Patients with diabetes mellitus have a predisposition toward developing chronic inflammatory demyelinating polyneuropathy, and this may also facilitate the formation of diabetic foot and cutaneous impairment, which are considered one of the most serious impairments of diabetes mellitus, with a prevalence of 4–10% in this population. Biomarkers research provides opportunities for the early diagnosis of these complications for specific treatments useful to prevent amputation and, therefore, physical inability and mental disturbance. The recent literature has suggested that glycemic levels may be a novel factor in the pathogenesis of diabetic foot complications and is an important mediator of axonal dysfunction. The aim of this systematic literary review is to determine whether hemoglobin A1c (HbA1c) is a positive predictor for diabetic foot peripheral neuropathy and its complications, such as foot cutaneous impairments. There is a lack of consensus regarding the effect of glycemic variability on diabetic foot peripheral neuropathy, unlike other complications such as retinopathy, nephropathy or micro/macrovascular pathology Methods: Relevant articles were searched in the Medline database using PubMed and Scopus and relevant keywords. The primary search terms used were “glycated hemoglobin” OR “HbA1c” AND “diabetic neuropathies” AND “Foot”. Results: A number of articles (336) were initially identified while searching the scientific literature regarding this topic, and 32 articles were selected and included in this review. Conclusions: This review highlights the role of HbA1c in diabetic foot peripheral neuropathy. Biomarkers play an important role in the decision-making process, and HbA1c levels are extensively used for diabetic foot clinical outcomes and settings, but biomarker research in diabetic foot peripheral neuropathy is in its infancy and will require careful attention to a number of factors and associations, since the consequences of DPN also include neurological alterations. HbA1c is an accurate and easy-to-administer test and can be an effective biomarker in establishing the diagnosis of diabetes, but future research should focus on standardizing the HbA1c level and selecting which DPN value and its correlated complications, such as foot cutaneous impairments, are the most informative. Full article

Background: Antimicrobial resistance (AMR) among Gram-negative pathogens, predominantly ESBL-producing clinical isolates, are increasing worldwide. The main aim of this study was to determine the prevalence of ESBL-producing clinical isolates, their antibiogram, and the frequency of ESBL genes (bla_TEM and bla_CTX-M) in the clinical samples from patients. Methods: A total of 1065 clinical specimens from patients suspected of heart infections were collected between February and August 2019. Bacterial isolates were identified on colony morphology and biochemical properties. Thus, obtained clinical isolates were screened for antimicrobial susceptibility testing (AST) using modified Kirby–Bauer disk diffusion method, while ESBL producers were identified by using a combination disk diffusion method. ESBL positive isolates were further assessed using conventional polymerase chain reaction (PCR) to detect the ESBL genes bla_TEM and bla_CTX-M. Results: Out of 1065 clinical specimens, 17.8% (190/1065) showed bacterial growth. Among 190 bacterial isolates, 57.4% (109/190) were Gram-negative bacteria. Among 109 Gram-negative bacteria, 40.3% (44/109) were E. coli, and 30.2% (33/109) were K. pneumoniae. In AST, 57.7% (n = 63) Gram-negative bacterial isolates were resistant to ampicillin and 47.7% (n = 52) were resistant to nalidixic acid. Over half of the isolates (51.3%; 56/109) were multidrug resistant (MDR). Of 44 E. coli, 27.3% (12/44) were ESBL producers. Among ESBL producer E. coli isolates, 58.4% (7/12) tested positive for the bla_CTX-M gene and 41.6% (5/12) tested positive for the bla_TEM gene. Conclusion: Half of the Gram-negative bacteria in our study were MDR. Routine identification of an infectious agent followed by AST is critical to optimize the treatment and prevent antimicrobial resistance. Full article

Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both cases, although the histology was that of clear cell carcinoma and undifferentiated carcinoma, respectively. Therefore, the cases were referred to as endometriosis-associated intestinal tumors (EIATs). Actionable variants (all frameshift mutations) were identified in tumor suppressor genes ARID1A, PTEN, and p53; however, no oncogenic variants were identified. Both cases were microsatellite stable. The patient with undifferentiated carcinoma exhibited hypermutator and homologous recombination deficiency phenotypes. The dominant mutation signatures were signature 30 (small subset of breast cancers) and 19 (pilocytic astrocytoma) in patient 1, and signature 5 (small subset of breast cancers) and 3 (breast, ovarian, and pancreatic cancers) in patient 2. Immunohistochemistry revealed positive CD8 and PD-1 expression in both patients; patient 1 also showed positive PDL-1 expression. Our results suggest that RSEAC is associated with variants of tumor suppressor genes as epigenetic alterations. Mutation signature-based whole-exome sequencing could be useful to select an adjuvant chemotherapy regimen. High CD8 and PD-1 expression in RSEAC suggests that immune checkpoint inhibitors are useful for treatment. Full article

Background: Epitestosterone [E] has for a long time been considered as a biologically inactive androgen. However, recently a distinct antiandrogenic activity of this naturally occurring endogenous epimer of Testosterone has been demonstrated. Especially the ratios of testosterone/epitestosterone (T/E) seem to be key as inhibition of epitestosterone on androgen activity was postulated. As in autism, a higher androgen activity was implied. We, therefore, suggested higher levels of T/E ratios of children with autism versus children with typical development. Methods: Urine probes of 22 girls with autism (BMI 18.7 ± 4.3; average age 12.3 ± 3.8 years) and a sample of 51 controls (BMI 17.0 ± 2.6; average age 11.9 ± 4 years), as well as 61 boys with autism (BMI 17.04 ± 2. average age 11.9 ± 2.5 years) and 61 control boys (BMI 17.0 ± 2.6; average age 11.1 ± 3.0 years), were analyzed with gas chromatography mass spectrometry. RESULTS: The average T/E ratio of all boys with autism was 2.5 ± 1.8 versus 2.4 ± 1.3 in boys with typical development, respectively. No significant difference between boys with autism versus boys with typical development could be detected (p = 0.977). In girls with autism, the average T/E ratio was 1.4 ± 0.9 versus 2.0 ± 1.4 in girls with typical development, whereby a significant difference could be detected (p = 0.0285). Further, polynomial analysis of the third degree were conducted, showing a dependence from age with reasonable coefficients of determination (0.075 < R² < 0.22, all samples). Discussion: As encompassing steroid hormone analysis are expensive and work-intensive, we hoped to find an easily applicable biomarker to support diagnostics in autism. However, as a relatively small sample of only 22 girls with autism were analyzed and menstrual cycle and pubertal status were only partly controllable through the matching of BMI and age, the question arises if it was an incidental finding. Nevertheless, one suggestion might be that epitestosterone has the effect of a competitive inhibition on the androgen receptor, which would probably help to explain the higher prevalence of autism in boys as compared to girls. Presumably, as no significant difference was detected in boys, this effect might not be as relevant from a steroid hormone perspective, and other effects such as altered 17/20-hydroxylase activity as previously shown in boys and girls with autism seem to have more relevance. Analysis of larger samples, including plenty of metabolites and enzymatic cascades, as well as the role of backdoor pathway activity of androgen synthesis of girls with autism, are demanded in order to validate current findings of altered steroid hormones in autism. Full article

With the approval and distribution of demonstrably safe COVID-19 vaccines bearing exceptionally high efficacy profiles, it may be tempting to envision a return to “normal” in the coming months. However, if there is one lesson to be learned from the ongoing pandemic, it is that, in a world of evolving zoonotic viruses, we must be better prepared for the next deadly outbreak. While the acute nature of the COVID-19 pandemic demanded a highly specific approach, it is advisable to consider the breadth of seemingly endless possibilities in our approach to managing the next inevitable occurrence of an outbreak. Though there is little chance of discovering a “magic pill” to combat all future pathogens, the highly conserved nature of non-surface viral proteins exposes an “Achilles’ heel” in the structural genome of viral pathogens. Herein, we consider the potential of targeting such proteins to develop broad-spectrum therapeutics for the future. To illustrate this point, we outline the therapeutic potential of targeting the nonstructural protein 16 methyltransferase, which is conserved across most coronaviruses. Full article

Purpose:To record the health promotion behaviors of family caregivers of stroke survivors, as well as potential determinants that could affect these behaviors. Methods: A cross-sectional study was carried out through home visits in the Attica region using the convenience sampling method. The studied population included 109 survivors who had suffered a stroke and experienced functional problems, and their 109 primary caregivers, who were family members, lived in the same house and were fully responsible for their care. The dependent variables were the caregivers’ health promotion behaviors, while the independent variables were the survivors and caregivers’ demographic characteristics, survivors’ functional capacity, depression, social support and changes in caregivers’ lives from caring. Results: Better health promotional behaviors were associated with the following: patient having advanced age and a high level of functionality, caregivers assessing their own state of health as “good”, greater social support, a higher educational level and a higher income level. In addition, more hours of patient care were associated with a less healthy lifestyle for caregivers. Conclusions: Promoting the health of family caregivers of stroke survivors is crucial for both survivors and caregivers. For this reason, it is of great importance to detect factors that affect the health promotion behaviors of caregivers in order to carry out appropriate interventions and improve their quality of life. Full article

Three important observations derived from the ongoing COVID-19 pandemic could result in the development of novel approaches to deal with it and avoid or at least minimize the occurrence and impact of future outbreaks. First, the dramatic increase in pandemics in the past decade alone suggests that the current relationship of humans with the environment is quickly becoming unstable, with potentially catastrophic consequences. In order to reduce the toll in life and property, we would need to shift our emphasis from control of nature to a symbiosis with nature. This, then, can become the new framework for dealing effectively with environmental issues such as climate change, whereby properly applied medical science would provide the necessary impetus for action. Second, the existence of superspreaders of infection among populations in this pandemic requires that we develop objective tests, most likely of a genetic nature, to identify them rather than apply indiscriminate and draconian controls across the board. Not identifying superspreaders in a timely fashion could allow this pandemic to turn into a black swan event, with a catastrophic impact on society. Third, we need to refocus our efforts in dealing with this pandemic from the virus itself to the human hosts. An objective morbidity risk index can be developed such that most of us can go about our daily business without the fear of becoming seriously ill, while measures can be implemented to protect those who are most vulnerable to this virus. These observations point clearly to a need for a paradigm shift. Full article

Chemo and radiation therapies are the most commonly used therapies for cancer, but they can induce DNA damage, resulting in the apoptosis of host cells. DNA double-stranded breaks (DSBs) are the most lethal form of DNA damage in cells, which are constantly caused by a wide variety of genotoxic agents, both environmentally and endogenously. To maintain genomic integrity, eukaryotic organisms have developed a complex mechanism for the repair of DNA damage. Researches reported that many cellular long noncoding RNAs (lncRNAs) were involved in the response of DNA damage. The roles of lncRNAs in DNA damage response can be regulated by the dynamic modification of N6-adenosine methylation (m6A). The cellular accumulation of DNA damage can result in various diseases, including cancers. Additionally, lncRNAs also play roles in controlling the gene expression and regulation of autophagy, which are indirectly involved with individual development. The dysregulation of these functions can facilitate human tumorigenesis. In this review, we summarized the origin and overview function of lncRNAs and highlighted the roles of lncRNAs involved in the repair of DNA damage. Full article

Background: This study aimed to evaluate the risk factors for circulatory shock and its impact on outcomes in patients hospitalized for salicylate intoxication. Methods: We used the National Inpatient Sample to identify patients hospitalized primarily for salicylate intoxication from 2003–2014. Circulatory shock was identified based on hospital diagnosis code for any type of shock or hypotension. We compared clinical characteristics, in-hospital treatments, outcomes, and resource use between patients with and without circulatory shock associated with salicylate intoxication. Results: Of 13,805 hospital admissions for salicylate intoxication, circulatory shock developed in 484 (4%) admissions. Risk factors for development of circulatory shock included older age, female sex, concurrent psychotropic medication overdose, anemia, congestive heart failure, volume depletion, rhabdomyolysis, seizure, gastrointestinal bleeding, and sepsis. Circulatory shock was significantly associated with increased odds of any organ failure and in-hospital mortality. Length of hospital stay and hospitalization cost was significantly higher in patients with circulatory shock. Conclusion: Approximately 4% of patients admitted for salicylate intoxication developed circulatory shock. Circulatory shock was associated with worse clinical outcomes and increased resource use. Full article

Suspicion of failure in the effectiveness of artemisinin-based combination therapies (currently the first-line treatment of malaria, worldwide) is leading to the unofficial use of alternative antimalarials, including chloroquine and sulfadoxine/pyrimethamine, across northern Nigeria. To facilitate evidence-based resistance management, antimalarial resistance mutations were investigated in Plasmodium falciparum multidrug resistance-1 (pfmdr1) and chloroquine resistance transporter (pfcrt), in isolates from Kano, northwestern Nigeria. Out of the 88 samples genotyped for pfmdr1 N86Y mutation using PCR/restriction fragment length polymorphism, one sample contained the 86Y mutation (86Y_frequency = 1.14%). The analysis of 610 bp fragments of pfmdr1 from 16 isolates revealed two polymorphic sites and low haplotype diversity (H_d = 0.492), with only 86 Y mutations in one isolate, and 184 F replacements in five isolates (184F_frequency = 31.25%). The analysis of 267 bp fragments of pfcrt isolates revealed high polymorphism (H_d = 0.719), with six haplotypes and seven non-synonymous polymorphic sites. Eleven isolates (61.11%) were chloroquine-resistant, CQR (C₇₂V₇₃I₇₄E₇₅T₇₆ haplotype), two of which had an additional mutation, D⁵⁷E. An additional sequence was CQR, but of the C₇₂V₇₃M₇₄E₇₅T₇₆ haplotype, while the rest of the sequences (33.33%) were chloroquine susceptible (C₇₂V₇₃M₇₄N₇₅K₇₆ haplotype). The findings of these well characterized resistance markers should be considered when designing resistance management strategies in the northwestern Nigeria. Full article

Background: The progression of chronic kidney disease (CKD) is concomitant with complications, including thyroid dysfunction, dyslipidemia and cardiovascular diseases. The aim of this study is to determine serum cystatin C levels, and the prevalence of vitamin D deficiency and thyroid dysfunction in CKD patients. Methods: A cross-sectional study was conducted involving 140 CKD patients (stages 1–5) that were referred to a renal clinic. Demographic data was collected and thyroid function tests, serum 25-OH-vitamin D, cystatin C levels, and routine biochemistry tests were determined using cobas 6000 analyzer. Results: 129 (92.1%) of CKD patients had elevated serum cystatin C levels and there was a stepwise increase from stage 1–5. Overt hypothyroidism was present in one patient and nine had subclinical hypothyroidism. There was a stepwise reduction in serum 25-OH-vitamin D levels from stage 2–5, 31 (22.1%) had vitamin D insufficiency and 31 (22.1%) presented with deficiency. Conclusions: 25-OH-vitamin D deficiency and thyroid disorders are exhibited in chronic kidney disease patients and the severity of the former rises with disease progression, as indicated by elevated cystatin C levels. Routine screening and timely intervention is recommended so as to reduce the risk of cardiovascular diseases. Full article

Although vegetables are beneficial for human health, in many countries, the recommended vegetable intake is not reached. To assess vegetable intake, it is important to understand vegetable consumption. Therefore, we conducted a cross-sectional and intervention study of 26 healthy individuals (50% women; 37.0 ± 8.9 years) and estimated vegetable intake on the basis of the cutaneous carotenoid level (CCL) with a noninvasive skin carotenoid sensor, considering that vegetable juice intake can increase CCL. Participants consumed vegetable juice containing 350 g of vegetables daily for 4 weeks. Blood carotenoid levels and CCL were measured for 12 weeks. Cross-sectional analysis showed a significant positive correlation between CCL and vegetable intake (r = 0.489). Vegetable juice consumption significantly increased CCL and the blood levels of α-carotene, β-carotene, and lycopene (p < 0.05). The correlation coefficient between the blood level and CCL for lycopene was smaller (r = 0.001) compared to that between the blood level and CCL for α-carotene (r = 0.523) and β-carotene (r = 0.460), likely because of bioavailability differences. In conclusion, noninvasive skin carotenoid measurements are effective for determining vegetable intake, and vegetable juice significantly increases CCL. Full article

Background: This study aimed to evaluate thrombotic microangiopathy’s (TMA) incidence, risk factors, and impact on outcomes and resource use in hospitalized patients with systemic lupus erythematosus (SLE). Methods: We used the National Inpatient Sample to construct a cohort of hospitalized patients with SLE from 2003–2014. We compared clinical characteristics, in-hospital treatments, outcomes, and resource use between SLE patients with and without TMA. Results: Of 35,745 hospital admissions for SLE, TMA concurrently presented or developed in 188 (0.5%) admissions. Multivariable analysis showed that age ≥ 40 years and Hispanics were significantly associated with decreased risk of TMA, whereas Asian/Pacific Islanders and history of chronic kidney disease were significantly associated with increased risk of TMA. TMA patients required more kidney biopsy, plasmapheresis, mechanical ventilation, and renal replacement therapy. TMA was significantly associated with increased risk of in-hospital mortality and acute conditions including hemoptysis, glomerulonephritis, encephalitis/myelitis/encephalopathy, hemolytic anemia, pneumonia, urinary tract infection, sepsis, ischemic stroke, seizure, and acute kidney injury. The length of hospital stays and hospitalization cost was also significantly higher in SLE with TMA patients. Conclusion: TMA infrequently occurred in less than 1% of patients admitted for SLE, but it was significantly associated with higher morbidity, mortality, and resource use. Full article

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%–42.5%), 14.5% (95%CI: 8.4%–23.7%), and 20.2% (95%CI: 15.4%–25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%–37.3%), 11.7% (95%CI: 8.4%–16.0%), and 20.2% (95%CI: 15.5%–26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%–29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD. Full article

Dogs are reservoirs of many zoonotic diseases. In Ethiopia, the majority of owned dogs are semi-stray, freely roaming in the community. Studies reporting dog borne zoonotic diseases are scarce in Ethiopia. This study was conducted to assess Dipylidium caninum infection in dogs and in children with gastrointestinal complaints in Bishoftu Town, Oromia. We collected 384 fecal samples from dogs presented to veterinary teaching hospital and 259 stool samples from children presented to Bishoftu Hospital for clinical examination. Samples were first macroscopically examined for the presence of proglotids, followed by microscopic examination for the presence of eggs with the direct smear following flotation technique. The prevalence of D. caninum was 21% (95% CI: 16.6–24.9) in dogs. Although not statistically significant (p > 0.05), higher prevalence was detected in adult (11.9%), local breed (17.7%), and male (12.6%) dogs compared to young (8.59%), exotic breed (2.86%), and females (7.81%), respectively. Dipylidium caninum was detected in a stool sample obtained from a three year-old child (0.4%, 1/259). This study showed that the prevalence of D. caninum in the dogs is high while it is rare in children. Although the prevalence in children is negligible in this study, the high proportion of infected dogs can pose a significant risk of infection in the general human population. Public health risk can be reduced by eliminating the semi-roaming of owned dogs and proper management of dogs with regular deworming and prevention of environmental contamination with dog feces. Similarly, raising public awareness about dog borne zoonoses and avoiding contact with dog feces are important. Full article

There are common clinical scenarios in chronic heart disease where no randomized controlled data exist to guide management, and it is likely that well-designed observational studies will have to be used to inform clinical practice. Showing the clinical applicability of this type of study design, using record linkage of population electronic health records, we have provided key observational evidence that use of renin–angiotensin-system (RAS) blockers is associated with better outcomes in patients with aortic stenosis and that metformin could be used safely as an antiglycemic drug in patients with diabetes and heart failure. Each of these pieces of underpinning research has made a major contribution to relevant international clinical practice guidelines, helped the Food and Drug Administration in their decision making and changed prescribing practice. Full article

Reproductive health is compromised during anorexia nervosa (AN). However, it is still unclear whether this medical complication is reversible after recovery from AN. The purpose of this paper was to conduct a systematic review of the major reproductive health outcomes in females after recovery from AN. The review was conducted in adherence to preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. Data were collated using meta-analysis and a narrative approach. Of the 1186 articles retrieved, five studies met the inclusion criteria and were reviewed. These studies monitored weight-restored females who had recovered from AN for a follow-up period of between six and 18 years. Their narrative analysis revealed that appropriate treatment of AN leads to the normalization of reproductive function, especially in terms of fertility, pregnancy, and childbirth rates. The meta-analysis confirmed this finding, where the pooled odds of childbirth rates between the AN group and the general population was not statistically significant (OR = 0.75, 95% CI: 0.43–1.29, p = 0.41). We conclude that if patients undergo appropriate eating-disorder treatment and weight restoration, it appears to be unlikely that reproductive health is affected by AN. However, since this finding is derived from only a few studies, it requires replication and confirmation. Full article

Many Geriatric Health Services Facilities in Japan may have continued outpatient rehabilitation by taking measures against infection even during the state of emergency caused by Coronavirus disease 2019 (COVID-19). The present study aimed to determine differences in physical and psychological states in rehabilitation outpatients (age, 83.5 ± 8.4 years) at a Geriatric Health Services Facility between the pre- and post-nationwide state of emergency in Japan. Physical outcomes were assessed with gait speed (GS), timed up and go test (TUG), handgrip strength (HG), and maximum phonation time (MPT). We used the Japanese version of the five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L) to assess patients’ quality of life (QoL) as the psychological state. The physical (GS, pre, 0.92, post, 0.92 s, p = 0.875; TUG, pre, 14.09, post, 14.14 s, p = 0.552; HG, pre, 19.42, post 19.70 kgf, p = 0.807; MPT, pre, 13.6, post, 13.8 s, p = 0.861) and psychological (EQ-5D-5L, pre, 0.73, post, 0.81, p = 0.064) states of the participants did not change significantly between the pre- and post-nationwide state of emergency. This was likely due to the continuance of outpatient rehabilitation in accordance with the facility’s policy while taking adequate safety precautions against COVID-19 infection. Full article