Gut Hormones in Health and Obesity: The Upcoming Role of Short Chain Fatty Acids

We are currently facing an obesity pandemic, with worldwide obesity rates having tripled since 1975. Obesity is one of the main risk factors for the development of non-communicable diseases, which are now the leading cause of death worldwide. This calls for urgent action towards understanding the underlying mechanisms behind the development of obesity as well as developing more effective treatments and interventions. Appetite is carefully regulated in humans via the interaction between the central nervous system and peripheral hormones. This involves a delicate balance in external stimuli, circulating satiating and appetite stimulating hormones, and correct functioning of neuronal signals. Any changes in this equilibrium can lead to an imbalance in energy intake versus expenditure, which often leads to overeating, and potentially weight gain resulting in overweight or obesity. Several lines of research have shown imbalances in gut hormones are found in those who are overweight or obese, which may be contributing to their condition. Therefore, this review examines the evidence for targeting gut hormones in the treatment of obesity by discussing how their dysregulation influences food intake, the potential possibility of altering the circulating levels of these hormones for treating obesity, as well as the role of short chain fatty acids and protein as novel treatments.     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Developing fMRI protocol for clinical use Comparison of 6 Arabic paradigms for brain language mapping in native Arabic speakers

Objectives:To assess a baseline assessment using developed functional magnetic resonance imaging (fMRI) language paradigms for Arabic-speakers.Methods:24-healthy right-handed volunteers scanned on a 3.0 Tesla MRI machine. For fMRI, a BOLD-sensitive sequence used to measure signals over time across 6 language paradigms: rhyming (RH), semantic category generations (SCG), silent word generation (SWG), verb generation picture (VGp), verb generation word (VGw), and verb generation audio (VGa). fMRI data was analyzed using FMRIB Software Library (FSL).Results:We found that VGa, SWG, VGw and VGp robustly activated language-related regions in the dominant hemisphere. RH and SCG failed to adequately define these activation regions but this may be related to the study’s preliminary nature and limitations. After assessment of their validity, considerable activation of the inferior frontal gyrus during VGa, SWG, VGw and VGp suggests that these paradigms have the potential for localizing of Broca’s area in native Arabic speakers.Conclusion:Set of well adapted, and evidence-based, fMRI paradigms were established for Arabic-speakers to enable accurate and sufficient localization and lateralization of the language area. After validation, these paradigms may provide sequences for accurate localization of brain language areas, and could be used as a presurgical evaluation tool.

Functional magnetic resonance imaging (fMRI) allows precise, and non-invasive, localization and lateralization of brain functions. Clinically, these techniques have considerable success, and hold great potential in the management of a variety of neurological disorders. One of the most promising clinical applications of fMRI is presurgical linguistic mapping.1-5 The 3 classical language areas that are involved in language production and processing are Broca’s and Wernicke’s areas, and angular gyrus. Wernicke’s area can be described as a receptive region, for processing and integrating auditory sensory information, while Broca’s area can be described as a productive region, for making vocal signals, and meaningful words or sentences. The latter includes pars opercularis and triangularis. The angular gyrus area is particularly involved in reading and transitioning between written and spoken forms of language. Injury to language regions produces noticeable clinical deficits, and the location of these regions may become difficult to assess without advanced anatomical imaging such as fMRI. Internationally, fMRI replaces the more invasive Wada test (also known as the intracarotid sodium amobarbital procedure) in lateralizing language and memory at some centers.6,7Language is a highly complex system that markedly varies across individuals. Patients native language affects brain activation responses during fMRI scans.8-13 As such, language paradigms for presurgical fMRI mapping should be developed and validated using native language paradigms. Language dominance of the left cerebral hemisphere has been well researched and established, but native language and social factors were also reported to play a key role in cortical association of verbal processing.8,14-16Although language localization using fMRI has been routinely used in western countries, and more recently in an Arabic country,17 studies clearly demonstrated that different cultures may process language in different manners, using different brain mechanisms.8,14-16 Existing language paradigms, created for non-Arabic speaking patients, require major modifications before applying them in examining native Arabic speakers.17Language lateralization is another broadly used clinical application of fMRI. Concordance with Wada test has long been demonstrated and validated in the literature using paradigms with various tasks such as verbal fluency, comprehension, and semantic judgment .18-21 These have shown that concordance with Wada test can reach 90% in temporal lobe epilepsy, especially in left-dominant patients. A slightly lower concordance was achieved in right-dominant patients. Although fMRI language lateralization works well for patients with typical language dominance, clinicians need to be careful when interpreting results of patients with atypical language representation.22Semitic languages such as Arabic differ from other languages in many aspects, including orthography (including diacritics), phonology, and syntax. Therefore, significant research in developing and validating language paradigms for Arabic is required. To our knowledge, very few studies in this domain have been carried out.17,23 One developed several language and memory paradigms in neurological patients, while emphasizing consideration for educational and cultural adjustments,17 and the other examined neuronal correlates of diacritics (vs. lack of thereof) in 11 healthy men.23We aim to establish tasks adapted to the Arabic language, that also reliably activate Broca’s and Wernicke’s areas in a relatively short scanning time. This study is a baseline assessment using 6 developed fMRI language paradigms for Arabic-speaking presurgical candidates. The desired outcome of this work is to create a set of Arabic language localization protocols, along with standard operating procedures.     

Assessment methods for the evaluation of vitiligo

There is no standardized method for assessing vitiligo. In this article, we review the literature from 1981 to 2011 on different vitiligo assessment methods. We aim to classify the techniques available for vitiligo assessment as subjective, semi‐objective or objective; microscopic or macroscopic; and as based on morphometry or colorimetry. Macroscopic morphological measurements include visual assessment, photography in natural or ultraviolet light, photography with computerized image analysis and tristimulus colorimetry or spectrophotometry. Non‐invasive micromorphological methods include confocal laser microscopy (CLM). Subjective methods include clinical evaluation by a dermatologist and a vitiligo disease activity score. Semi‐objective methods include the Vitiligo Area Scoring Index (VASI) and point‐counting methods. Objective methods include software‐based image analysis, tristimulus colorimetry, spectrophotometry and CLM. Morphometry is the measurement of the vitiliginous surface area, whereas colorimetry quantitatively analyses skin colour changes caused by erythema or pigment. Most methods involve morphometry, except for the chromameter method, which assesses colorimetry. Some image analysis software programs can assess both morphometry and colorimetry. The details of these programs (Corel Draw, Image Pro Plus, AutoCad and Photoshop) are discussed in the review. Reflectance confocal microscopy provides real‐time images and has great potential for the non‐invasive assessment of pigmentary lesions. In conclusion, there is no single best method for assessing vitiligo. This review revealed that VASI, the rule of nine and Wood’s lamp are likely to be the best techniques available for assessing the degree of pigmentary lesions and measuring the extent and progression of vitiligo in the clinic and in clinical trials.     

Clinical Outcomes of Patients Hospitalized with Coronavirus Disease 2019 (COVID-19) in Boston

BackgroundOutcomes of hospitalized patients with COVID-19 have been described in health systems overwhelmed with a surge of cases. However, studies examining outcomes of patients admitted to hospitals not in crisis are lacking.ObjectiveTo describe clinical characteristic and outcomes of all patients with COVID-19 who are admitted to hospitals not in crisis, and factors associated with mortality in this population.DesignA retrospective analysisParticipantsIn total, 470 consecutive patients with COVID-19 requiring hospitalization in one health system in Boston from January 1, 2020 to April 15, 2020.Main MeasuresWe collected clinical outcomes during hospitalization including intensive care unit (ICU) admission, receipt of mechanical ventilation, and vasopressors. We utilized multivariable logistic regression models to examine factors associated with mortality.Key ResultsA total of 470 patients (median age 66 [range 23–98], 54.0% male) were included. The most common comorbidities were diabetes (38.5%, 181/470) and obesity (41.3%, 194/470). On admission, 41.9% (197/470) of patients were febrile and 60.6% (285/470) required supplemental oxygen. During hospitalization, 37.9% (178/470) were admitted to the ICU, 33.6% (158/470) received mechanical ventilation, 29.4% (138/470) received vasopressors, 16.4% (77/470) reported limitations on their desire for life-sustaining therapies such as intubation and cardiopulmonary resuscitation, and 25.1% (118/470) died. Among those admitted to the ICU (N=178), the median number of days on the ventilator was 10 days (IQR 1–29), and 58.4% (104/178) were discharged alive. Older age (OR=1.04, P<0.001), male sex (OR=2.14, P=0.007), higher comorbidities (OR=1.20, P=0.001), higher lactate dehydrogenase on admission (2nd tertile: OR=4.07, P<0.001; 3rd tertile: OR=8.04, P<0.001), and the need for supplemental oxygen on admission (OR=2.17, P=0.014) were all associated with higher mortality.ConclusionsThe majority of hospitalized patients with COVID-19 and those who received mechanical ventilation survived. These data highlight the need to examine public health and system factors that contribute to improved outcomes for this population.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06622-x.     

Thoracic imaging outcomes in COVID-19 survivors

The coronavirus disease 2019 (COVID-19) pandemic presents a significant global public health challenge. One in five individuals with COVID-19 presents with symptoms that last for weeks after hospital discharge, a condition termed “long COVID”. Thus, efficient follow-up of patients is needed to assess the resolution of lung pathologies and systemic involvement. Thoracic imaging is multimodal and involves using different forms of waves to produce images of the organs within the thorax. In general, it includes chest X-ray, computed tomography, lung ultrasound and magnetic resonance imaging techniques. Such modalities have been useful in the diagnosis and prognosis of COVID-19. These tools have also allowed for the follow-up and assessment of long COVID. This review provides insights on the effectiveness of thoracic imaging techniques in the follow-up of COVID-19 survivors who had long COVID.     

Investigations into the Mass Spectrometric Method for the Determination of the Mode of Termination in Radical Polymerization

The fraction of termination by disproportionation, λ, in radical polymerization may be determined by a mass spectrometric (MS) analysis of the resulting polymer. It is subjected to an array of stringent consistency checks, working with polymerizations of methyl methacrylate at 85 °C in three different solvents and with four different initiators. λ is shown to be unaffected by the choice of initiator, initiator concentration, or isoviscous solvent. These findings serve to allay any fears about the method being undermined by effects such as primary radical termination or chain transfer to solvent, thereby establishing its robustness. At the same time, direct evidence for the occurrence of chain transfer to the solvent methyl isobutyrate is uncovered, and the importance of knowing other rate‐parameter values accurately, if λ is to be determined accurately, is illustrated. By carrying out MS analyses, it is concluded that electrospray ionization with time‐of‐flight detection gives the best results for the present purpose.

     

Prevalence of post-traumatic stress disorder during the COVID-19 pandemic in Saudi Arabia

BackgroundThe coronavirus diseases of 2019 (COVID-19) pandemic was classified as one of the worst pandemics in the 21st century. Its rapid transmission, unpredicted mortality rate, and the uncertainty surrounding its transmission method have evoked additional fear and anxiety. Nonetheless, to the best of our knowledge, no prior study has explored PTSD prevalence three months after the start of the quarantine procedures in Saudi Arabia nor has examined PTSD prevalence by three different methods.ObjectiveThis observational cross-sectional study aimed to identify the prevalence, severity, and influencing factors of PTSD in different regions of Saudi Arabia three months after the onset of the quarantine procedures related to the COVID-19 pandemic.MethodsThrough the month of June 2020, 1374 people (49.05% men and 50.95% women) completed a 35-item, 10-minute online. The prevalence of PTSD was measured using PCL-S (specific for COVID-19) that assesses the 17 symptoms of PTSD. Resilience was measured using 2-items Arabic version of the Connor-Davidson Resilience Scale 2 (CD-RISC 2).ResultsWe calculated the prevalence by three methods, namely, PTSD cut-off score, criteria, and combined, and the prevalence was 22.63%, 24.8%, and 19.6%, respectively. Female participants showed higher prevalence than male. As well, participants who were either tested positive or suspected of having been infected with COVID-19 showed higher PTSD prevalence. Higher resilience was associated with lower PTSD prevalence.ConclusionsThis was the first study to report PTSD prevalence by three differential methods three months after the onset of the quarantine procedures related to the COVID-19 pandemic in Saudi Arabia. We observed a significant impact of the COVID-19 pandemic in the Saudi population; therefore, great attention should be performed in implementing new procedures that deal with the highlighted risk factors, especially in vulnerable groups, to overcome the psychological impact of the COVID-19 pandemic.     

Orthodontic treatment and referral patterns: A survey of pediatric dentists,general practitioners,and orthodontists

Objective

This study aims to assess the orthodontic diagnostic skills, referral patterns, and the perceptions of orthodontic benefits of pediatric and general dentists in comparison with orthodontists.

Materials and methods

Two online surveys were e-mailed to pediatric dentists, general dentistry practitioners, and orthodontists registered as members of the Saudi Dental Society and the Saudi Orthodontic Society. The surveys included questions about the type of orthodontic treatment provided, referral trends, and timing; presumed benefits associated with successful orthodontic treatment; and diagnosis and treatment plans of seven cases representing different malocclusions.

Results

In total, 25 orthodontists, 18 pediatric dentists, and 14 general practitioners completed the survey. Only 38.8% of pediatric dentists and 7.1% of general practitioners reported that they practiced orthodontics clinically. The perceptions of the three groups toward the benefits of orthodontic treatment were comparable in the psychosocial areas. However, the orthodontists perceived significantly lesser effects of orthodontic treatment on the amelioration of temporomandibular disorder (TMD) symptoms. Pediatric dentists tended to rate the need and urgency of treatment higher, while general practitioners tended to rate the need of treatment lower. The selected treatment plans for three early malocclusion cases showed the greatest discrepancies between the orthodontists and the other two groups.

Conclusions

The orthodontists consistently and significantly downplayed the perceived benefit of orthodontic treatment to reduce TMD symptoms. Also, while there was a similarity in the diagnosis, there were notable differences in the proposed treatment approaches, perceived treatment need, and timing of intervention between the three groups of practitioners.