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Volume 9, September

Med. Sci., Volume 9, Issue 4 (December 2021) – 15 articles

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Review
Nutrients, Cognitive Function, and Brain Aging: What We Have Learned from Dogs
Med. Sci. 2021, 9(4), 72; https://doi.org/10.3390/medsci9040072 - 18 Nov 2021
Viewed by 289
Abstract
Due to a difference in genetics, environmental factors, and nutrition, just like in people, dogs age at different rates. Brain aging in people and dogs share similar morphological changes including irreversible cortical atrophy, cerebral amyloid angiopathy, and ventricular enlargement. Due to severe and [...] Read more.
Due to a difference in genetics, environmental factors, and nutrition, just like in people, dogs age at different rates. Brain aging in people and dogs share similar morphological changes including irreversible cortical atrophy, cerebral amyloid angiopathy, and ventricular enlargement. Due to severe and irreversible brain atrophy, some aging dogs develop cognitive dysfunction syndrome (CDS), which is equivalent to dementia or Alzheimer’s disease (AD) in people. The risk factors and causes of CDS in dogs have not been fully investigated, but age, gender, oxidative stress, and deficiency of sex hormones appears to be associated with increased risk of accelerated brain aging and CDS in dogs. Both AD and CDS are incurable diseases at this moment, therefore more efforts should be focused on preventing or reducing brain atrophy and minimizing the risk of AD in people and CDS in dogs. Since brain atrophy leads to irreversible cognitive decline and dementia, an optimal nutritional solution should be able to not only enhance cognitive function during aging but also reduce irreversible brain atrophy. Up to now, only one nutritional intervention has demonstrated both cognition-enhancing benefits and atrophy-reducing benefits. Full article
(This article belongs to the Special Issue Nutrition and the Ageing Brain)
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Review
Wound Healing and Therapy in Soft Tissue Defects of the Hand and Foot from a Surgical Point of View
Med. Sci. 2021, 9(4), 71; https://doi.org/10.3390/medsci9040071 - 13 Nov 2021
Viewed by 169
Abstract
Wounds and tissue defects of the hand and foot often lead to severe functional impairment of the affected extremity. Next to general principles of wound healing, special functional and anatomic considerations must be taken into account in the treatment of wounds in these [...] Read more.
Wounds and tissue defects of the hand and foot often lead to severe functional impairment of the affected extremity. Next to general principles of wound healing, special functional and anatomic considerations must be taken into account in the treatment of wounds in these anatomical regions to achieve a satisfactory reconstructive result. In this article, we outline the concept of wound healing and focus on the special aspects to be considered in wounds of the hand and foot. An overview of different treatment and dressing techniques is given with special emphasis on the reconstruction of damaged structures by plastic surgical means. Full article
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Case Report
Removal of a Giant Cyst of the Left Ovary from a Pregnant Woman in the First Trimester by Laparoscopic Surgery under Spinal Anesthesia during the COVID-19 Pandemic
Med. Sci. 2021, 9(4), 70; https://doi.org/10.3390/medsci9040070 - 13 Nov 2021
Viewed by 223
Abstract
This paper reports a case of a 21 year old primigravida at 6 weeks gestation, suffering from important abdominal pain, who was admitted into the medical center with a giant cyst of 28 × 20 cm on her left ovary. A torsion of [...] Read more.
This paper reports a case of a 21 year old primigravida at 6 weeks gestation, suffering from important abdominal pain, who was admitted into the medical center with a giant cyst of 28 × 20 cm on her left ovary. A torsion of the ovarian cyst was suspected. Her COVID-19 status was unknown. In view of the emergency of the situation and the COVID-19 pandemic, laparoscopy in spinal anesthesia was performed. The patient remained conscious during the surgical intervention and tolerated it well apart from a slight dyspnea, which was easily eliminated by changing her body position and decreasing the pneumoperitoneum pressure. The ovarian cyst was removed by enlarging the trocar incision. The patient recovered with neither incident nor pregnancy loss. COVID-19-related complications can induce adverse pregnancy outcomes. Under general anesthesia, patients with COVID-19 are at risk of severe pneumonia and of passing their infection to the medical personnel. To avoid such complications in non-specialized centers, laparoscopy should be performed in regional anesthesia. Laparoscopy in spinal anesthesia can be performed safely on pregnant patients by placing them in the proper position, using a low pneumoperitoneum, and monitoring the hemodynamics. During early pregnancy, general anesthesia induces a higher risk of teratogenic effects and of miscarriage. Full article
(This article belongs to the Special Issue New Insights in Pregnancy-Related Disorders)
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Article
Trabecular Bone Score and Bone Mineral Density in Postmenopausal Women with Morbid Obesity—A Clinical Paradox
Med. Sci. 2021, 9(4), 69; https://doi.org/10.3390/medsci9040069 - 09 Nov 2021
Viewed by 262
Abstract
Obesity has long been considered to have a protective effect on bone, but specific complications in those with morbid obesity are known to have a detrimental impact on bone architecture. We aimed to study the bone microarchitecture (TBS—trabecular bone score) and bone mineral [...] Read more.
Obesity has long been considered to have a protective effect on bone, but specific complications in those with morbid obesity are known to have a detrimental impact on bone architecture. We aimed to study the bone microarchitecture (TBS—trabecular bone score) and bone mineral density (BMD) in postmenopausal women with morbid obesity compared to obese and non-obese age-matched women. Eighty-five consecutive postmenopausal women with morbid obesity (body mass index (BMI) ≥ 35 kg/m2) were enrolled and compared to age-matched obese (n = 80) and non-obese postmenopausal controls (n = 85). The BMD and TBS were assessed in all subjects using a Hologic-QDR 4500-W Discovery-A DXA scanner. The mean BMD (gm/cm2) at the femoral neck in women with morbid obesity was found to be significantly lower as compared to the age-matched postmenopausal obese controls (0.723 versus 0.762, p-value = 0.002). The BMD at the lumbar spine and hip showed similar trends but were not statistically significant. The bone microarchitecture was found to be significantly lower in those with morbid obesity (1.205) as compared to the other two groups (obesity 1.244; non-obese 1.228) (p < 0.013). Though obesity was associated with a better bone density and bone microarchitecture in postmenopausal women, a paradoxical lower value was seen in those with morbid obesity. Full article
(This article belongs to the Special Issue Contemporary Endocrinology)
Opinion
Post-Coronavirus Disease-2019 (COVID-19): Toward a Severe Multi-Level Health Crisis?
Med. Sci. 2021, 9(4), 68; https://doi.org/10.3390/medsci9040068 - 08 Nov 2021
Viewed by 275
Abstract
There were already numerous challenges facing the healthcare system prior to the ongoing coronavirus disease-2019 (COVID-19) pandemic. Although we look forward to ending this pandemic, it is still expected that the healthcare system will face further challenges leading to a multi-level health crisis. [...] Read more.
There were already numerous challenges facing the healthcare system prior to the ongoing coronavirus disease-2019 (COVID-19) pandemic. Although we look forward to ending this pandemic, it is still expected that the healthcare system will face further challenges leading to a multi-level health crisis. Indeed, after the COVID-19 pandemic, there will still be COVID-19 active cases and those left with health problems following COVID-19 infection who will be of a particular impact. In addition, we also have the health problems that either emerged or worsened during COVID-19, especially with the reduced ability of the healthcare system to take care of many non COVID-19 patients during the COVID-19 pandemic. Such expected evolution of the situation highlights the necessity for the decision-makers to consider applying serious reforms and take quick measures to prevent a post-COVID-19 health crisis. Full article
(This article belongs to the Section Translational Medicine)
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Perspective
Sodium Chloride, Migraine and Salt Withdrawal: Controversy and Insights
Med. Sci. 2021, 9(4), 67; https://doi.org/10.3390/medsci9040067 - 30 Oct 2021
Viewed by 381
Abstract
This paper examines evidence implicating migraine headache as a withdrawal symptom of excessive sodium chloride intake. Emerging research in food addiction posits that food and drug addictions share common features, such as withdrawal symptoms. Salt (sodium chloride) meets the criteria for the diagnosis [...] Read more.
This paper examines evidence implicating migraine headache as a withdrawal symptom of excessive sodium chloride intake. Emerging research in food addiction posits that food and drug addictions share common features, such as withdrawal symptoms. Salt (sodium chloride) meets the criteria for the diagnosis of substance dependence, including withdrawal in which the substance is used to relieve withdrawal symptoms. The premonitory symptoms of migraine include food cravings for salty foods, which can alleviate migraine pain. Edema, possibly related to large amounts of salt consumed in binge eating, can cause approximately four pounds of retained fluid. This amount of fluid is similar to the fluid retained before the onset of migraine headache, which may be accompanied by polyuria. This paper proposes that inhibited withdrawal from highly processed food intake, rich in salt, mediates an association between increased sodium chloride intake and relief from migraine headache pain. The relief from withdrawal symptoms could also be a mediating factor that explains the controversial findings inversely associating dietary sodium intake with migraine history. Moreover, the withdrawal of retained sodium and edema related to the use of nonsteroidal anti-inflammatory drugs may elucidate a potential mechanism in medication overuse headache. Further research is needed to investigate the pain experienced from sodium chloride withdrawal in migraine headache. Full article
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Article
Prospective Evaluation of Low-Dose External Beam Radiotherapy (LD-EBRT) for Painful Trapeziometacarpal Osteoarthritis (Rhizarthrosis) on Pain, Function, and Quality of Life to Calculate the Required Number of Patients for a Prospective Randomized Study
Med. Sci. 2021, 9(4), 66; https://doi.org/10.3390/medsci9040066 - 27 Oct 2021
Viewed by 314
Abstract
Background: Retrospective studies have described the effectiveness of low-dose radiotherapy (LD-EBRT) in painful arthrosis of small finger joints, but two recent prospective studies have yielded ambiguous results. To generate accurate data for the planning of a trial, we conducted a prospective, monocentric, observational [...] Read more.
Background: Retrospective studies have described the effectiveness of low-dose radiotherapy (LD-EBRT) in painful arthrosis of small finger joints, but two recent prospective studies have yielded ambiguous results. To generate accurate data for the planning of a trial, we conducted a prospective, monocentric, observational study to describe the effects of LD-EBRT as precisely as possible. Methods: Twenty-five consecutive patients with symptomatic trapeziometacarpal (TMC) arthrosis were irradiated with 6 × 0.5 Gy. Before, 3, and 12 months after LD-EBRT, we assessed subjective endpoints (modified “von-Pannewitz score”, 10-point visual analogue scale (VAS), “patient-rated wrist evaluation” (PRWE)), and objective measurements (“active range of motion” (AROM), Kapandji index, grip strength, pinch grip). Results: At 3/12 months, 80%/57% reported partial and 4%/18% complete remission according to the “von-Pannewitz” score. VAS “overall pain” significantly decreased from a median of seven (IQR 4) at baseline to three (IQR 6; p = 0.046) and to two (IQR 2; p = 0.013). Similar results were obtained for VAS “pain during exercise”, VAS “pain during daytime”, and VAS “function”. “PRWE overall score” was reduced from 0.5 at baseline (SD 0.19) to 0.36 (SD 0.24, p = 0.05) and to 0.27 (SD 0.18, p = 0.0009). We found no improvements of the objective endpoints (AROM, Kapandji, grip strength) except for flexion, which increased from 64° (SD 12°) at baseline to 73° (SD 9.7°, p = 0.046) at 12 months. Conclusions: We recommend the PRWE score as a useful endpoint for further studies for this indication. To prove a 15% superiority over sham irradiation, we calculated that 750 patients need to be prospectively randomized. Full article
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Article
Mortality and Clinical Outcomes among Patients with COVID-19 and Diabetes
Med. Sci. 2021, 9(4), 65; https://doi.org/10.3390/medsci9040065 - 26 Oct 2021
Viewed by 326
Abstract
Background Diabetes mellitus (DM) is a decisive risk factor for severe illness in coronavirus disease 2019 (COVID-19). India is home to a large number of people with DM, and many of them were infected with COVID-19. It is critical to understand the impact [...] Read more.
Background Diabetes mellitus (DM) is a decisive risk factor for severe illness in coronavirus disease 2019 (COVID-19). India is home to a large number of people with DM, and many of them were infected with COVID-19. It is critical to understand the impact of DM on mortality and other clinical outcomes of COVID-19 infection from this region. Aims The primary objective of our study was to analyze the mortality rate in people with DM infected with COVID-19. The secondary objectives were to assess the effect of various comorbidities on mortality and study the impact of DM on other clinical outcomes. Methods This is a retrospective study of COVID-19 infected patients admitted to a tertiary care hospital in north India in the early phase of the pandemic. Results Of the 1211 cases admitted, 19 were excluded because of incomplete data, and 1192 cases were finally considered for analysis. DM constituted 26.8% of total patients. The overall mortality rate was 6.1%, and the rate was 10.7% in the presence of diabetes (p < 0.01, OR 2.55). In univariate analysis, increased age, chronic kidney disease (CKD), coronary artery disease (CAD), stroke, and cancer were associated with mortality. On multiple logistic regression, the independent predictors of mortality were CAD, CKD, and cancer. Breathlessness and low SpO2 at presentation, extensive involvement in CXR, and elevated ANC/ALC ratio were also significantly associated with mortality. Conclusions The presence of comorbidities such as DM, hypertension, CAD, CKD, and cancer strongly predict the risk of mortality in COVID-19 infection. Early triaging and aggressive therapy of patients with these comorbidities can optimize clinical outcomes. Full article
(This article belongs to the Special Issue Contemporary Endocrinology)
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Article
The Route of Motor Recovery in Stroke Patients Driven by Exoskeleton-Robot-Assisted Therapy: A Path-Analysis
Med. Sci. 2021, 9(4), 64; https://doi.org/10.3390/medsci9040064 - 26 Oct 2021
Viewed by 310
Abstract
Background: Exoskeleton-robot-assisted therapy is known to positively affect the recovery of arm functions in stroke patients. However, there is a lack of evidence regarding which variables might favor a better outcome and how this can be modulated by other factors. Methods: [...] Read more.
Background: Exoskeleton-robot-assisted therapy is known to positively affect the recovery of arm functions in stroke patients. However, there is a lack of evidence regarding which variables might favor a better outcome and how this can be modulated by other factors. Methods: In this within-subject study, we evaluated the efficacy of a robot-assisted rehabilitation system in the recovery of upper limb functions. We performed a path analysis using a structural equation modeling approach in a large sample of 102 stroke patients (age 63.6 ± 13.1 years; 61% men) in the post-acute phase. They underwent 7 weeks of bilateral arm training assisted by an exoskeleton robot combined with a conventional treatment (consisting of simple physical activity together with occupational therapy). The upper extremity section of the Fugl–Meyer (FM-UE) scale at admission was used as a predictor of outcome, whereas age, gender, side of the lesion, days from the event, pain scale, duration of treatment, and number of sessions as mediators. Results: FM-UE at admission was a direct predictor of outcome, as measured by the motricity index of the contralateral upper limb and trunk control test, without any other mediating factors. Age, gender, days from the event, side of lesion, and pain scales were independently associated with outcomes. Conclusions: To the best of our knowledge, this is the first study assessing the relationship between clinical variables and outcomes induced by robot-assisted rehabilitation with a path-analysis model. We define a new route for motor recovery of stroke patients driven by exoskeleton-robot-assisted therapy, highlighting the role of FM-UE at admission as a useful predictor of outcome, although other variables need to be considered in the time-course of disease. Full article
(This article belongs to the Special Issue Advances in Neurorehabilitation: Robotics, Virtual Reality and Beyond)
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Review
Epidemiology of Melanoma
Med. Sci. 2021, 9(4), 63; https://doi.org/10.3390/medsci9040063 - 20 Oct 2021
Cited by 1 | Viewed by 461
Abstract
Melanoma accounts for 1.7% of global cancer diagnoses and is the fifth most common cancer in the US. Melanoma incidence is rising in developed, predominantly fair-skinned countries, growing over 320% in the US since 1975. However, US mortality has fallen almost 30% over [...] Read more.
Melanoma accounts for 1.7% of global cancer diagnoses and is the fifth most common cancer in the US. Melanoma incidence is rising in developed, predominantly fair-skinned countries, growing over 320% in the US since 1975. However, US mortality has fallen almost 30% over the past decade with the approval of 10 new targeted or immunotherapy agents since 2011. Mutations in the signaling-protein BRAF, present in half of cases, are targeted with oral BRAF/MEK inhibitor combinations, while checkpoint inhibitors are used to restore immunosurveillance likely inactivated by UV radiation. Although the overall 5-year survival has risen to 93.3% in the US, survival for stage IV disease remains only 29.8%. Melanoma is most common in white, older men, with an average age of diagnosis of 65. Outdoor UV exposure without protection is the main risk factor, although indoor tanning beds, immunosuppression, family history and rare congenital diseases, moles, and obesity contribute to the disease. Primary prevention initiatives in Australia implemented since 1988, such as education on sun-protection, have increased sun-screen usage and curbed melanoma incidence, which peaked in Australia in 2005. In the US, melanoma incidence is not projected to peak until 2022–2026. Fewer than 40% of Americans report practicing adequate protection (sun avoidance from 10 a.m.–4 p.m. and regular application of broad-spectrum sunscreen with an SPF > 30). A 2-4-fold return on investment is predicted for a US sun-protection education initiative. Lesion-directed skin screening programs, especially for those at risk, have also cost-efficiently reduced melanoma mortality. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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Article
Common Pitfalls in Ewing Sarcoma and Desmoplastic Small Round Cell Tumor Diagnosis Seen in a Study of 115 Cases
Med. Sci. 2021, 9(4), 62; https://doi.org/10.3390/medsci9040062 - 15 Oct 2021
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Abstract
Ewing sarcoma (ES), “Ewing-like sarcoma” (ELS) and desmoplastic small round cell tumors (DSRCT) can masquerade as other tumor types, particularly neuroendocrine neoplasms and receive inappropriate treatment. We retrieved 115 cases of ES, ELS and DSRCT seen over 17 years in a tertiary center. [...] Read more.
Ewing sarcoma (ES), “Ewing-like sarcoma” (ELS) and desmoplastic small round cell tumors (DSRCT) can masquerade as other tumor types, particularly neuroendocrine neoplasms and receive inappropriate treatment. We retrieved 115 cases of ES, ELS and DSRCT seen over 17 years in a tertiary center. An initial misdiagnosis or incomplete diagnosis occurred in 6/93 (6.4%) of ES/ELS and 5/22 (22.7%) of DSRCT cases. The most frequent misdiagnosis was small cell neuroendocrine carcinoma. While any misdiagnosis or incomplete classification is almost certainly multifactorial, the most common identified reason for erroneous/incomplete initial reporting was expression of neuroendocrine markers. Other contributing factors included keratin expression, older patient age and apparently unusual tumor location. Most patients treated with a non-sarcoma chemotherapy regimen expired, while those who received a sarcoma-related regimen were alive as of last evaluation. Increased awareness of this diagnostic pitfall is needed in evaluating cases of round cell malignancies. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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Article
Universal Access to Advanced Imaging and Healthcare Protection: UHC and Diagnostic Imaging
Med. Sci. 2021, 9(4), 61; https://doi.org/10.3390/medsci9040061 - 27 Sep 2021
Viewed by 447
Abstract
Universal Health Coverage (UHC) is a set of principles adopted by the World Health Organization (WHO) aimed to guarantee access to primary care for the entire world population through a range of essential health services without neglecting the diagnostic aspect. Italy is one [...] Read more.
Universal Health Coverage (UHC) is a set of principles adopted by the World Health Organization (WHO) aimed to guarantee access to primary care for the entire world population through a range of essential health services without neglecting the diagnostic aspect. Italy is one of the signatory states, which means that diagnostic services should be appropriated and exigible throughout the national territory equally. Our research analyzed and identified the main criticalities in terms of age, territorial distribution, and technological and health appropriateness of installed Computed Tomography (CT) needed to meet the principles of UHC. Data analyzed in our study were published by Assobiomedica at the end of 2016 and by COCIR, which included and investigated the installed fleet of diagnostic equipment in the Italian sanitary system and in various European countries. The 6th point of the Alma Ata Declaration defines the concept of “primary health care”, which includes the importance of the diagnostic phase in the Italian health care system to provide Essential Levels of Assistance (LEA). It is clear from our studies that the technology at the national level is not adequate to satisfy the UHC principles or the European criteria, with negative effects on the diagnostic standards and on advanced screenings. This study conducted on the installed CTs in Italy at the end of 2016 confirms the persistence of progressive aging that has been recorded for several years in the health facilities of the country and suggests incentive policies for the replacement of obsolete equipment, which represent a form of investment rather than a cost, due to the nature of the expenditure itself, one-off and amortizable over time. Full article
Article
Clinically Distinct Subtypes of Acute Kidney Injury on Hospital Admission Identified by Machine Learning Consensus Clustering
Med. Sci. 2021, 9(4), 60; https://doi.org/10.3390/medsci9040060 - 24 Sep 2021
Cited by 1 | Viewed by 718
Abstract
Background: We aimed to cluster patients with acute kidney injury at hospital admission into clinically distinct subtypes using an unsupervised machine learning approach and assess the mortality risk among the distinct clusters. Methods: We performed consensus clustering analysis based on demographic information, principal [...] Read more.
Background: We aimed to cluster patients with acute kidney injury at hospital admission into clinically distinct subtypes using an unsupervised machine learning approach and assess the mortality risk among the distinct clusters. Methods: We performed consensus clustering analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 4289 hospitalized adult patients with acute kidney injury at admission. The standardized difference of each variable was calculated to identify each cluster’s key features. We assessed the association of each acute kidney injury cluster with hospital and one-year mortality. Results: Consensus clustering analysis identified four distinct clusters. There were 1201 (28%) patients in cluster 1, 1396 (33%) patients in cluster 2, 1191 (28%) patients in cluster 3, and 501 (12%) patients in cluster 4. Cluster 1 patients were the youngest and had the least comorbidities. Cluster 2 and cluster 3 patients were older and had lower baseline kidney function. Cluster 2 patients had lower serum bicarbonate, strong ion difference, and hemoglobin, but higher serum chloride, whereas cluster 3 patients had lower serum chloride but higher serum bicarbonate and strong ion difference. Cluster 4 patients were younger and more likely to be admitted for genitourinary disease and infectious disease but less likely to be admitted for cardiovascular disease. Cluster 4 patients also had more severe acute kidney injury, lower serum sodium, serum chloride, and serum bicarbonate, but higher serum potassium and anion gap. Cluster 2, 3, and 4 patients had significantly higher hospital and one-year mortality than cluster 1 patients (p < 0.001). Conclusion: Our study demonstrated using machine learning consensus clustering analysis to characterize a heterogeneous cohort of patients with acute kidney injury on hospital admission into four clinically distinct clusters with different associated mortality risks. Full article
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Review
Early Gestational Diabetes Mellitus: Diagnostic Strategies and Clinical Implications
Med. Sci. 2021, 9(4), 59; https://doi.org/10.3390/medsci9040059 - 23 Sep 2021
Viewed by 404
Abstract
Preexisting diabetes mellitus (DM) should be ruled out early in pregnancy in those at risk. During screening, a significant proportion of women do not reach the threshold for overt DM but fulfill the criteria used for diagnosing conventional gestational DM (cGDM). There is [...] Read more.
Preexisting diabetes mellitus (DM) should be ruled out early in pregnancy in those at risk. During screening, a significant proportion of women do not reach the threshold for overt DM but fulfill the criteria used for diagnosing conventional gestational DM (cGDM). There is no consensus on the management of pregnancies with intermediate levels of hyperglycemia thus diagnosed. We have used the term early gestational DM (eGDM) for this condition and reviewed the currently available literature. Fasting plasma glucose (FPG), oral glucose tolerance test, and glycated hemoglobin (HbA1c) are the commonly employed screening tools in early pregnancy. Observational studies suggest that early pregnancy FPG and Hba1c correlate with the risk of cGDM and adverse perinatal outcomes. However, specific cut-offs, including those proposed by the International Association of the Diabetes and Pregnancy Study Group, do not reliably predict the development of cGDM. Emerging data, though indicate that FPG ≥ 92 mg/dL (5.1 mmol/L), even in the absence of cGDM, signals the risk for perinatal complication. Elevated HbA1c, especially a level ≥ 5.9%, also correlates with the risk of cGDM and worsened outcome. HbA1c as a diagnostic test is however besieged with the usual caveats that occur in pregnancy. The studies that explored the effects of intervention present conflicting results, including a possibility of fetal malnutrition and small-for-date baby in the early treatment group. Diagnostic thresholds and glycemic targets in eGDM may differ, and large multicenter randomized controlled trials are necessary to define the appropriate strategy. Full article
(This article belongs to the Special Issue Contemporary Endocrinology)
Review
Critical Role of Caveolin-1 Loss/Dysfunction in Pulmonary Hypertension
Med. Sci. 2021, 9(4), 58; https://doi.org/10.3390/medsci9040058 - 22 Sep 2021
Viewed by 568
Abstract
Pulmonary hypertension (PH) is a rare disease with a high morbidity and mortality rate. A number of systemic diseases and genetic mutations are known to lead to PH. The main features of PH are altered vascular relaxation responses and the activation of proliferative [...] Read more.
Pulmonary hypertension (PH) is a rare disease with a high morbidity and mortality rate. A number of systemic diseases and genetic mutations are known to lead to PH. The main features of PH are altered vascular relaxation responses and the activation of proliferative and anti-apoptotic pathways, resulting in pulmonary vascular remodeling, elevated pulmonary artery pressure, and right ventricular hypertrophy, ultimately leading to right heart failure and premature death. Important advances have been made in the field of pulmonary pathobiology, and several deregulated signaling pathways have been shown to be associated with PH. Clinical and experimental studies suggest that, irrespective of the underlying disease, endothelial cell disruption and/or dysfunction play a key role in the pathogenesis of PH. Endothelial caveolin-1, a cell membrane protein, interacts with and regulates several transcription factors and maintains homeostasis. Disruption of endothelial cells leads to the loss or dysfunction of endothelial caveolin-1, resulting in reciprocal activation of proliferative and inflammatory pathways, leading to cell proliferation, medial hypertrophy, and PH, which initiates PH and facilitates its progression. The disruption of endothelial cells, accompanied by the loss of endothelial caveolin-1, is accompanied by enhanced expression of caveolin-1 in smooth muscle cells (SMCs) that leads to pro-proliferative and pro-migratory responses, subsequently leading to neointima formation. The neointimal cells have low caveolin-1 and normal eNOS expression that may be responsible for promoting nitrosative and oxidative stress, furthering cell proliferation and metabolic alterations. These changes have been observed in human PH lungs and in experimental models of PH. In hypoxia-induced PH, there is no endothelial disruption, loss of endothelial caveolin-1, or enhanced expression of caveolin-1 in SMCs. Hypoxia induces alterations in membrane composition without caveolin-1 or any other membrane protein loss. However, caveolin-1 is dysfunctional, resulting in cell proliferation, medial hypertrophy, and PH. These alterations are reversible upon removal of hypoxia, provided there is no associated EC disruption. This review examined the role of caveolin-1 disruption and dysfunction in PH. Full article
(This article belongs to the Special Issue Beyond Lipid Rafts and Caveolae: Caveolins in Disease)
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