Background: Acute high-altitude (HA) exposure results in blood pressure (BP) and cardiac function variations in most subjects, some of whom suffer from acute mountain sickness (AMS). Several previous studies have found that cardiovascular function indicators are potentially correlated with AMS.Objectives: This study aims to examine HA-induced cardiovascular adaptations in AMS patients and compare them with healthy subjects. It also aims to investigate the relationship between cardiovascular function indicators and AMS, as well as to provide some insightful information about the prevention and treatment of AMS.Methods: Seventy-two subjects were enrolled in this cohort study. All the subjects ascended Litang . They were monitored by a 24-h ambulatory blood pressure (ABP) device and underwent echocardiography examination within 24 h of altitude exposure. The 2018 Lake Louise questionnaire was used to evaluate AMS.Results: Acute mountain sickness group consisted of more women  and fewer smokers . Compared with subjects without AMS, subjects with AMS had lower pulse pressure (PP)  and lower effective arterial elastance (Ea) . Multivariate regression indicated that female sex , lower daytime PP , and lower Ea  at low altitude (LA) were independent risk factors for AMS. Combined daytime PP and Ea at LA had a high predictive value for AMS . Correlation analysis showed that AMS-induced headache correlated with daytime PP  and nighttime PP at LA .Conclusion: Our study demonstrated that AMS patients had a lower PP and Ea at LA. These baseline indicators of vasodilation at LA were closely associated with AMS, which may explain the higher headache severity in subjects with higher PP at LA. An increasing number of people have access to high-altitude (HA) areas for various reasons. However, HA is associated with hypobaric and hypoxic conditions and can induce a series of cardiovascular adaptations  and arterial elastance (Ea), which can be easily measured noninvasively, are important for determining the systolic and diastolic compliance of blood vessels. It has been previously shown that higher PP is a risk factor for cardiovascular and cerebrovascular events, such as ischemic stroke  and echocardiography at both low altitude (LA) and HA in AMS patients and non-AMS controls. We sought to determine whether there was a relationship between differential cardiovascular adaptation in HA and AMS. Moreover, we sought to provide some insights on the prevention and treatment of AMS.www.chictr.org.cn (ChiCTR-TRC-No.1900025728).Ninety-one subjects (32 women and 59 men) were included in this prospective observational cohort study that was performed in Chengdu, China, in 2019. Informed consent was obtained, and all subjects underwent a comprehensive medical examination before the expedition to LA . Information on cigarette smoking and alcohol history was collected from all participants. Subjects underwent ABP monitoring and echocardiography both at LA and HA . Exclusions were listed as follows: (1) Any clinical conditions that may affect HA-adaptation, including known pulmonary diseases, cardiovascular diseases, hematological diseases, (2) use of any oral medication. Ten subjects were excluded due to the above and another nine subjects were excluded due to lack of data. In total, 72 subjects were included, all of whom were volunteers who signed written informed consent. This study was conducted in agreement with the Declaration of Helsinki and was approved by the Human Ethics Committee of the Xinqiao Hospital, Third Military Medical University  which was registered at Two well-trained cardiovascular physicians recorded BP data using an ABP measurement device . The BP cuff was applied to the nondominant arm on a weekday morning and was removed 24 h later. All participants were asked to remain still during the measurement. The subjects were instructed to avoid unusual physical activities, and follow a standard schedule at both locations, LA and HA. Daytime and nighttime were defined as 6:00 to 22:00 and 22:00 to 6:00, respectively  to acquire LV data. Images were saved digitally for subsequent offline analysis using QLAB software . Measurements of LV dimensions and volumes were performed by a computerized analysis software system. Ejection fraction (EF) was calculated by the LV volume data. Mitral inflow pattern from the tips level was analyzed for peak early diastolic velocity (E) as well as late diastolic velocity (A) and E/A. Mitral annulus early diastolic velocity (e′) was measured at the septal and lateral mitral annulus and the E/e′ ratio was calculated by the mean septal E/e′ ratio and mean lateral E/e′ ratio. Effective Ea and end-systolic elastance (Ees) were computed by the formulas: SBP × 0.9/stroke volume and SBP × 0.9/end-systolic volume (ESV), whereas ventricular-arterial decoupling (VAC) was the ratio of Ea and Ees  was used to assess AMS 8 h after arriving at HA. Participants completed a four-item questionnaire with the assistance of an experienced physician. The questions involved the presence of headache, dizziness or lightheadedness, gastrointestinal symptoms, and fatigue. Each question had four possible responses ranging from 0 to 3, according to the severity of the symptoms . AMS was defined as a total score ≥3 with at least 1 point from headache . Corresponding results were listed in the t-test, while the data that did not fit a normal distribution were analyzed by the Mann–Whitney U-test. Categorical data were presented as percentages (%) and were compared by the chi-square test, continuity correction, or Fisher's exact test, as appropriate. Binary and multivariate logistic regression was used to predict the risk factors of AMS, and receiver operating characteristic (ROC) curve was computed to evaluate the effectiveness of the prediction. Given the collinearity between variables and the number of subjects available, variables for inclusion were carefully chosen in our model. In addition, due to headache being the core symptom of AMS, we used a multiple linear regression model to evaluate the relationship between the risk factors of AMS and HA-related headache. Statistical significance was assumed at p < 0.05. Statistical analyses were performed by using SPSS software 26 .Continuous variables were presented as mean ± standard deviation. Differences in measurements between men and women with normal distribution were tested using an independent sample p = 0.001) but a lower rate of smokers . The score of AMS and the percentage of AMS-related symptoms were also significantly higher in the AMS group  and a lower daytime SBP  at LA. Interestingly, although DBP was similar, daytime and nighttime PP were significantly lower in AMS subjects when compared with non-AMS subjects at LA . After arriving at HA, PP increased in the AMS group but declined in the non-AMS group. Furthermore, there was no obvious difference in ARV between the two groups both at LA and at HA  also significantly increased, whereas SpOecreased . No statnd at HA .p = 0.005) and Ea  while the difference of VAC was not obvious between the two groups at LA. Ea varied more in the AMS group after HA exposure but the difference did not reach statistical significance (End-diastolic volume (EDV) and ESV decreased significantly in all subjects after HA exposure. E/A and E/e′ declined but LV torsion and untwisting rate increased. This indicated that diastolic relaxation was not acutely impaired. Both Ees and Ea increased in the whole cohort after arriving at HA . There wificance .p = 0.035) was associated with increased risk of AMS. Smoking , male sex , higher daytime SBP , higher daytime PP , higher nighttime PP , higher Ees , and higher Ea  were all associated with decreased incidence of AMS (p = 0.024), lower daytime PP , and lower Ea   . ROC cur= 0.015) .R = −0.401, p < 0.001) and nighttime PP at LA   , which iOur study demonstrated that variations of ABP and cardiac function occur on acute HA exposure in both healthy and AMS subjects and analyzed the correlation between cardiovascular indicators and AMS. Interestingly, we found that the baseline levels of PP and Ea at LA, which represent vascular compliance, have good predictive value for AMS. This might explain the significant association between these factors and HA-induced headache.AMS is diagnosed by nonspecific symptoms that occur a few hours after exposure to altitudes of ≥2,500 m in unacclimatized subjects . The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.This study was conducted in agreement with the Declaration of Helsinki and was approved by the Human Ethics Committee of the Xinqiao Hospital, Third Military Medical University  which registered at ReC, JY, and LH worked on the conception of the study. ReC, MS, YY, JK, FY, CH, RaC, and LH contributed to the data collection. CL and JY checked the data. ReC and MS performed the statistical analysis. JY and ReC drafted the manuscript. YD, XG, CL, HT, JZ, and LH reviewed the manuscript. All authors have read and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Aortic stenosis (AS) and diabetes mellitus (DM) are both progressive diseases that if left untreated, result in significant morbidity and mortality. Several studies revealed that the prevalence of DM is substantially higher in patients with AS and, thus, the progression from mild to severe AS is greater in those patients with DM. DM and common comorbidities associated with both diseases, DM and AS, increase patient management complexity and make aortic valve replacement the only effective treatment. For that reason, a better understanding of the pathogenesis underlying both these diseases and the relationships between them is necessary to design more appropriate preventive and therapeutic approaches. In this review, we provided an overview of the main aspects of the relationship between AS and DM, including common comorbidities and risk factors. We also discuss the established treatments/therapies in patients with AS and DM. Aortic stenosis (AS), of which Degenerative is the most common form (DAS), is the valvular heart disease that most often requires surgical intervention in developed countries . The devHypertension, hypercholesterolemia and diabetes mellitus (DM) are among the diseases/factors seen to influence the progression of both atherosclerosis and DAS. Both type 1 and type 2DM (T1DM and T2DM) accelerate the development of atherosclerosis, which is not only due to the hyperglycaemia produced, but also, to the associated insulin resistance, dyslipidaemia, etc. In addition, T2DM induces a marked inflammatory response and increased lipid accumulation. These mechanisms also affect the development of DAS and they are associated with hypertrophic left ventricular remodelling, increased left ventricle mass, left ventricle end-systolic dimension and reduced systolic function. All these processes indicate that DM has an adverse effect on cardiac function and, indeed, AS patients with DM have been seen to have significantly worse left ventricle diastolic function . TherefoDAS is typically asymptomatic for long periods, up to several years, and from the time of diagnosis disease progression is unavoidable, evolving rapidly with a poor prognosis. Thus, finding new therapeutic options to treat this disease is one of its greatest challenges today. As DM influences the survival of DAS patients, careful risk stratification is required to adopt the best strategy to manage each patient. If we also take into account that there is no single parameter that allows us to adequately predict disease evolution, all the information available must be considered when taking decisions in clinical practice. Despite all the efforts to date, the management of DAS is complex as the only effective treatment is aortic valve replacement through either a surgical (SAVR) or transcatheter (TAVI) intervention . Recent In terms of pharmacological treatments, studies have been carried out, both with statins, and with other drugs related to calcium and phosphate metabolism, yet there are still no therapies capable of slowing down or altering calcification . Valve cBoth DM and AS commonly occur in the elderly population, and while there is evidence that the prevalence of DM is substantially greater in patients with AS, the full effects of DM on the long-term prognosis of patients with AS remains unclear. Some cross-sectional observational studies revealed that DM is associated with an increased risk of AV calcification ,11, yet Nowadays, it seems clear that DAS and DM are associated, yet the prevalence of diabetes in the DAS population varies greatly in different studies. DAS was reported in 41% of diabetics , althougThe existing controversies may reflect the different characteristics of the cohorts examined in each study, with different basal clinical characteristics and nationalities. Nationalities are important as different cultures and lifestyles affect the prevalence of DM. In fact, the leading three risk factors for diabetes are high body mass index (BMI), dietary risks and ambient particulate matter pollution . Data frp < 0.001 for both) [N-acetylglucosamine [DAS is now considered an active process with AV calcification representing a terminal event. Various pathogenic processes are now recognised as key drivers of AV stenosis and mineralization , such asor both) . Furtheror both) . The putcosamine  and altecosamine ,29, althIn a murine model genetically modified to produce DAS, the dysmetabolic state of T2DM, as well as a diabetogenic diet ,31, contThe coexistence of two or more pathological conditions, defined as multimorbidity, is a key priority for global health. The prevalence of multimorbidity has been estimated to be 55–98%, and it is associated with poorer outcomes in terms of disease management and treatment decisions ,41. AccoHypertension involves pathophysiological mechanisms such as the upregulation of the renin–angiotensin–aldosterone system (RAAS), endothelium dysfunction/oxidative stress, activation of the sympathetic nervous system (SNS), as well as activation of the immune system . HyperteChronic kidney disease (CKD) is a very prevalent condition worldwide   and therDyslipidemia is well established as a cardiovascular risk factor, and it has been estimated that more than 50% of the adult population worldwide has dyslipidemia . DyslipiObesity is a multifactorial disease, and it is considered to be another factor that could increase the risk of AS. Although there are studies that produced conflicting results ,65,66, aMetabolic syndrome involves the accumulation of several risk factors for cardiovascular diseases and DM . MetabolFinally, additional comorbidities in DAS and DM increase the risk of complications, affecting patient management. Thus, a multifactorial approach is necessary to diminish the frequency of adverse events and to establish adequate treatment strategies.Risk prediction in AS patients remains an important challenge to cardiologists, especially for asymptomatic patients. Current guidelines generally recommend a conservative strategy based on careful observation, waiting until indications for AV replacement emerge ,76. NeveHence, it is important to improve risk scores that define potentially high-risk groups that could benefit from other strategies or treatments. To date, risk stratification is mainly based on clinical characteristics such as age and cardiovascular risk factors, imaging studies such as transthoracic echocardiogram and cardiac magnetic resonance imaging (cMRI), and stress testing . Severe Currently, risk prediction scores for AS do not include metabolomic and proteomic data, although these approaches provide biochemical profiles focused on the characterization of the products of gene transcription. In fact, metabolites and protein biomarkers are powerful tools in managing different diseases, including errors of metabolism in newborns , cancer In T2DM patients, the association between poor glycaemic control and cardiovascular events is a well-established fact. Long-term glucose control reduces 25% of microvascular events in T2DM but it does not affect macrovascular events  and stroke). Several drugs have been developed to achieve effective glycaemic control in T2DM . In factp = 0.04 for superiority). The secondary end-points were also significantly reduced in the patients that received empagliflozin, with a 38% relative risk reduction (RRR) for cardiovascular death, a 32% RRR for death from any cause and a 35% RRR for HF-related hospitalization. Furthermore, empagliflozin is the first glucose-lowering agent that significantly reduces HF hospitalization and slows renal disease progression in DM patients. In a large, randomized trial [SGLT2-is delay the progression of microvascular changes, thus affecting T2DM patients and improving arterial stiffness. The recent EMPAREG OUTCOME trial proposed a major therapeutic breakthrough in the treatment of T2DM patients . Patiented trial  that incDespite the remarkable cardiac benefits of SGLT2-is, their underlying mechanism of action remains unclear. It seems that the metabolic effects are likely to be responsible for the reduction in cardiovascular mortality and HF hospitalization, improved glycaemic control, or decreased body weight and blood pressure. Moreover, tight glycaemic control previously failed to reduce either mortality or HF . It is mp = 0.06) [Canagliflozin, another SGLT2-is, significantly reduced the primary composite end-point of cardiovascular mortality, non-fatal MI, and non-fatal stroke by 14% in the CANVAS program . Empagli = 0.06) . Like th = 0.06) . Hence,  = 0.06) . However = 0.06)  conclude = 0.06) .In summary, SGLT2-is are the latest class of oral anti-hyperglycaemic agents available to treat patients with T2DM. Their novel mechanism of action makes these medications an intriguing option for patients throughout the natural history of T2DM and as a possible adjunct therapy for T1DM with close supervision. SGLT2-is have demonstrated non-inferiority and additional metabolic benefits, thus preserving and enhancing Beta-cell function. The clinical trials involving SGLT2-is have significantly improved cardiac outcomes in T2DM patients and they seem to show a class effect, with empagliflozin being the first glucose-lowering agent that significantly reduces HF, mortality, hospitalization and renal disease progression in diabetic patients .The professional organizations that guide the management of diabetes are the American Diabetes Association (ADA), the European Association for the Study of Diabetes (EASD), the American Association of Clinical Endocrinology/American College of Endocrinology (AACE/ACE), and the Endocrine Society and American College of Physicians (ACP). All these organizations agree on individualizing therapy through a patient-centred approach to guide the choice of medication. Based on recent findings from cardiovascular outcome trials, the consensus report guides healthcare professionals as to how to manage hyperglycaemia in patients with atherosclerotic cardiovascular disease, CKD and HF. The consensus also considers patients without atherosclerotic cardiovascular disease (ASCVD) or CKD, and the need to minimize hypoglycaemia and weight gain, thereby promoting weight loss. The ADA and AACE/ACE published updated recommendations for the management of patients with T2DM in their latest guidelines (2018). Moreover, the European Society of Cardiology, in collaboration with the EASD, released updated guidelines for diabetes, prediabetes and heart disease in 2019, recommending SGLT2-is and GLP-1 agonists as first-line therapies for people with diabetes who have heart disease or are at risk of heart disease . AlthougTreatment of diabetic patients with severe AS using anti-diabetic medication, in the form of both oral tablets and insulin, may target the valve or the myocardium. In theory, specific medical therapy should halt AS progression, reduce its haemodynamic repercussions on LV function and remodelling, and improve clinical outcomes. However, none of the current medications used in patients with AS to treat cardiac disease or comorbidities appear to affect the survival of patients with AS, nor have they been proven to slow down the course of the disease . The onlp < 0.01) and 3 years (56.9% vs. 65.9% vs. 67.9%: adj. p < 0.05) after TAVI. However, insulin-treated diabetes was not identified as an independent risk factor for higher mortality in the 1st  and 3rd years  after multivariable adjustment [p < 0.001). This mortality was more strongly associated with insulin treated diabetics  than non-insulin-treated diabetics  [Continuous improvements in surgical approaches and techniques, including minimally invasive AV replacement and increased use of new tissue (stented or sutureless) valves, might to some extent explain the conflicting results regarding AV replacement in diabetic patients. In a careful review of the literature surrounding the outcome of SAVR or TAVI interventions in diabetic patients, the analysis in the PARTNER trial showed that diabetic patients have a lower all-cause mortality after TAVI than after SAVR . In the justment . Similarjustment . Moreovejustment ,119. By = 0.052) .Despite the many studies referred to above, the optimal treatment for severe AS in both non-diabetic and diabetic patients remains unclear. As such, several trials are currently investigating the early/elective interventional approaches to treat asymptomatic severe AS patients.At present, the data have revealed an association between AS and DM, and that DM has a detrimental effect on the QoL and survival of AS patients. Despite the continuing search for novel therapeutic approaches to date, the only effective treatment is aortic valve replacement. More studies are needed to identify approaches that will help delay the progression of these diseases, thus improving the prognosis and evolution of patients with AS and DM.


The authors present a retrospective, observational case study of seven patients, who presented with retained Intra-Orbital Foreign Bodies (IOrbFBs) following penetrating orbital injury at a tertiary eye hospital over a period of one year. Cases were reviewed for epidemiological features, mechanism of injury, nature of foreign body, clinical features, imaging modality, associated complications, management outcomes, and the final prognosis. The mean age of presentation was 27.43 years. Amongst the seven patients, two were children (aged <10 years). The male : female ratio was 4 : 3. Of the seven retained IOrbFBs, two were plastic, two wooden, and three metallic in nature  injury, and one with knife). Two out of seven had no light perception at presentation. The periocular location of the foreign bodies was inferior in 4 cases and medial in 3 cases. Computed Tomography scan confirmed the diagnosis in five cases and Magnetic Resonance Imaging (MRI) was diagnostic in one. Surgical intervention was done in five cases, and two cases were managed conservatively. The authors conclude that favourable outcome can be achieved even without surgical removal in cases of inert metallic/inorganic IOrbFBs. The properties of plastic FBs can frequently render them invisible on imaging, or they may mimic chronic inflammatory conditions like tuberculosis. Long-standing wooden IOrbFBs evade identification radiologically due to prolonged hydration. The ultimate choice of intervention must be individualised, weighing the risks of retention against the risk of iatrogenic damage. Ocular trauma is a significant cause of blindness all over the world. Approximately 16% cases of orbital trauma are associated with a foreign body [This is a retrospective analysis of seven patients, diagnosed with retained IOrbFBs following penetrating injury, who presented to a tertiary eye hospital in New Delhi, India, between December 2018-19. The epidemiological characteristics, clinical features, mechanism of injury, nature of foreign body, diagnostic imaging, associated complications, management outcome, and the long-term prognosis were evaluated.). The mean age of presentation was 27.43 years. Amongst the seven patients, two were children (aged <10 years). The male : female ratio was 4 : 3. Of the seven retained IOrbFBs, two were plastic foreign bodies, two wooden, and three metallic in nature  injury, and one injury with knife). The time of presentation varied from as early as three hours to a delayed presentation of three years. Only one of these patients was asymptomatic with a Best-Corrected Visual Acuity (BCVA) of 20/20 whereas one of them was diagnosed as Traumatic Orbital Apex Syndrome (TOAS) with a retained posterior foreign body (FB) and no light perception (NLP). Surgical intervention was recommended in six patients. The periocular location of the foreign body was inferior in 4 cases and medial in 3 cases. Three patients presented with features of inflammation including discharging sinuses. Traumatic optic neuropathy was seen in two patients (cases 1 and 2). Initial Computed Tomography (CT) scan could confirm the diagnosis in five cases whereas in one case, a repeat scan was helpful. MRI was diagnostic in one case (Seven patients diagnosed with IOrbFB were studied . The meaone case .Staphylococcus aureus and negative for AFB (Acid Fast Bacilli) staining. CT scan of the orbit was suggestive of soft tissue thickening with inflammatory changes more prominent in the extraconal, medial compartment of the right orbit. No abscess or foreign body could be identified. Empirical treatment resulted in clinical improvement. However, there was persistence of discharging sinus on the superomedial aspect of the right orbit. A review of the scan was requested, and a linear non-metallic FB running posteriorly along the medial orbital wall was identified. Surgical exploration was done, and a cylindrical plastic FB, measuring 30 mm × 3 mm, was successfully removed  in the right eye. Fundoscopy was suggestive of right optic atrophy. The left eye was unremarkable. A history of trauma to the right eye, while playing with a pen 5 months prior to presentation, was present. A provisional diagnosis of orbital cellulitis was made, and the patient was started on broad-spectrum antibiotics . Purulent discharge, sent for culture and sensitivity examination, from the superomedial aspect of the orbit was positive for  removed . The patA 10-year-old male presented with sudden diminution of vision in the right eye for the past six days, following trauma from a ballpoint pen while playing at home. On examination, the right eye had NLP. An entry wound, 6 mm below the right lower lid, was noted. Right EOMs were limited in all gazes with ptosis, accompanied by hypoesthesia along the right forehead and upper lid region. A grade II RAPD with disc pallor was noted in the right eye. The rest of the examination was unremarkable. Initial Non-Contrast Computed Tomography (NCCT) scan was inconclusive. A repeat scan revealed a nonmetallic linear FB, 24 mm × 5 mm, lying in the posterior orbit. It was extraconal, posteriorly reaching up to the superior orbital fissure (SOF), inferiorly lifting the inferior rectus belly, and abutting the ipsilateral optic nerve. Fracture of the right orbital floor with fat herniation was also visualised. Magnetic Resonance Imaging (MRI) orbit further confirmed the CT findings. A Flash-Visual Evoked Potential (VEP) showed prolonged latency and low P-wave amplitude in the right eye. A confirmatory diagnosis of right TOAS was made. The patient was advised surgical removal of the IOrbFB due to its compressive effects and the FB being a potential source of infection. However, the patient's family refused surgery in view of increased perioperative morbidity and possibility of no significant gain in vision. Complete resolution of ptosis with full and free EOMs in the right eye was seen at a follow-up of 10 months with no change in BCVA .A 27-year-old female presented with painful swelling in both eyes. At presentation, she was disoriented to time, place, and person. Her husband gave a history of gunshot injury few hours back. On examination, circumferential limbal perforation with uveal tissue prolapse was noted in the left eye with no light perception (NLP). The right eye had lower lid swelling and a vision of 20/200 with vitreous hemorrhage and limited extraocular movements in upgaze. The patient was referred to the neurosurgery emergency department for adequate systemic management. NCCT scan of the head, orbit, and paranasal sinuses revealed a metallic density foreign body (suggestive of bullet) in relation to right orbital floor and in close proximity to the inferior rectus muscle with fat entrapment. It also showed fracture of the anterior and posterior wall of the frontal sinus, bilateral nasal bone and septum, and bilateral ethmoid along with fracture of the medial wall, lateral wall, and floor of the right orbit. Comminuted fracture of frontal bone on the left side involving the roof, medial wall, and floor of the left orbit was seen with no obvious entrapment of fat or muscle . The patHer right eye was initailly planned for orbital floor reconstruction with foreign body removal.A final visual acuity of 20/40 was, however, achieved with conservative management at one-year follow-up. Right extraocular movements were restored with no diplopia or significant enophthalmos.3.4.A 30-year-old male with BB injuries at multiple sites and an entry wound at the glabella presented for ophthalmic evaluation within six hours of injury. An NCCT scan was suggestive of a metallic FB in the anterior orbit, adjacent to the left medial rectus. On surgical exploration, the FB could not be retrieved, and a coexisting lower canalicular injury was repaired with silicon tube intubation. The postoperative CT scan was suggestive of posterior migration of the foreign body. No further intervention was attempted. The BCVA was 20/20 OU, pre- as well as post-operatively. No extraocular motility limitations were seen.A 35-year-old female presented with intermittent pain, discharge, and swelling in the left eye for three years with acute exacerbation of symptoms for 15 days. On examination, the left eye was hypotropic with associated chemosis, congestion, and limited extraocular movements in all gazes. The BCVA was 20/20 OD and 5/200 OS. The patient was started on empirical antibiotic therapy. Imaging was suggestive of a well-defined lesion in the posterior aspect of the left orbit between lateral and inferior recti with post-contrast enhancement. On surgical exploration, a flat wooden IOrbFB (3.8 cm × 0.5 cm) was obtained. On further questioning, the patient vaguely recalled an episode of trauma to the left eye while cutting firewood 3 years back. After completion of antibiotic therapy, there was complete resolution of inflammation and improvement in extraocular motility in the left eye along with restoration of BCVA to 20/20 OU.A 36-year-old female presented with recurrent swelling in the left lower lid. There was an associated history of trauma to the left eye while cutting a wooden log 8 months back. The lacrimal apparatus was patent on syringing. Ultrasonography features were suggestive of left inferomedial orbital abscess. The abscess was drained surgically, and a wooden foreign body, measuring 2 cm × 1 cm × 0.3 cm, was retrieved.A 50-year-old male presented with a history of physical assault with a knife to the right eye 1 day back. There was an entry wound 7 to 8 mm below the right lower lid, and the BCVA was 20/20 OD. No impairment of ocular motility was seen. NCCT orbit was suggestive of a linear metallic IOrbFB running along the right orbital floor which was successfully removed with surgical intervention.Cases of trauma involving the orbit and periorbital region are commonly encountered in clinical settings. Both trivial and severe cases may be accompanied by a FB retained in the orbit. However, the diagnosis and management of a retained IOrbFB are frequently a challenging exercise for the treating ophthalmologist. In patients who present early, clinical suspicion and appropriate imaging may be conclusive in most cases. However, a late presentation with a vague history of trivial trauma can prove to be particularly difficult. Studies have documented a time lapse of up to 50 years . In our The presenting features of IOrbFBs include clinical signs of orbital cellulitis, orbital hematoma, proptosis, impaired motility, diplopia, visual field loss, orbital abscess, optic neuropathy/atrophy, SOF syndrome, or TOAS. It is imperative to enquire about history of trauma in such patients. The most common presenting features in our series were the signs of orbital inflammation , impaired motility, and disc pallor. IOrbFBs can settle in the orbit via transocular route and can have concurrent intraocular foreign body along with vitreous hemorrhage, retinal/choroidal detachment, uveitis, endophthalmitis, and panophthalmitis. The most interesting presentation in one of our cases was a plastic FB associated with chronic suppurative discharging sinus masquerading as a tuberculous osteomyelitis.The nature of FB plays a decisive role in diagnosis and management. On the basis of composition, foreign bodies in the orbit can be metallic , inorganic non-metallic , or organic  . A plainCT scan, a more readily available imaging modality with a shorter acquisition time, is the investigation of choice . Thin axMRI is considered the investigation of choice for organic FBs. In cases with a definitive history of injury with organic matter, it may be considered as the initial investigation of choice. For all other situations, initial CT to rule out metallic FB is advisable. An MRI scan allows for better assessment of soft tissue damage. Unlike CT, wood is usually hypointense relative to intraorbital fat on both T1- and T2-weighted sequences and does not show gadolinium enhancement. In T1-weighted images (T1-WI), a wooden FB gives a more uniform signal and is more discernible as compared to T2-weighted imaging (T2-WI). The possibility of getting motion artefacts is also higher in T2-WI , 16.In our study, CT scan helped to clinch the diagnosis in 5 patients while MRI was the diagnostic requirement in only one case of wooden FB. Two of our patients had plastic IOrbFBs, in whom diagnostic difficulties were encountered during imaging. Initially missed on CT, the FB was identified on subsequent scans. This may be attributed to the highly variable radiolucency of plastic. In some cases, plastic has been seen to resemble bone, while in others, it has mimicked air , 17.All patients with retained IOrbFBs should be given anti-tetanus prophylaxis and broad-spectrum antibiotics. For wooden IOrbFBs, initiation of empirical antifungal therapy has been advocated, owing to the frequent polymicrobial nature of the associated infection . The decOne patient in our study had injury with a BB pellet (case 4). It should be noted that orbital injury with a projectile metal such as a pellet or bullet can extend up to the cranial cavity. Shock waves from the projectile may cause chorioretinitis sclopetaria, even in the absence of direct trauma to the eyeball . Air gunForeign objects at the orbital apex and those extending beyond the superior orbital fissure are frequently associated with optic neuropathy and permanent damage to the neurovascular structures. Owing to their proximity to the apex, they are likely to contribute to significant ocular morbidity. FBs at the apex may present as Superior Orbital Fissure syndrome (SOF), OAS, Cavernous Sinus Syndrome, or may be completely inert . SurgicaThus, in all cases of suspected IOrbFB, detailed examination of the eye and appropriate imaging should be performed to evaluate the site, size and nature of the FB, and the resultant damage incurred. Patients with IOrbFBs must be well-informed regarding the choices and the prognosis. Ultimately, inputs from both the ophthalmologist as well as the patient are important for the final decision. In the present study, both conservative and surgical management strategies have been adopted in different situations and based on these experiences, the authors conclude that every case behaves uniquely, and a tailored approach should be adopted by the surgeon .


Salinization of freshwater is increasingly observed in regions where chloride de-icing salts are applied to the roads in winter, but little is known about the effects on microbial communities. In this study, we analyzed the planktonic microbiomes of four lakes that differed in degree of urbanization, eutrophication and salinization, from an oligotrophic reference lake with no surrounding roads, to a eutrophic, salinized lake receiving runoff from a highway. We tested the hypothesis that an influence of road salts would be superimposed on the effects of season and trophic status. We evaluated the microbial community structure by 16S rRNA sequencing for Bacteria, and by four methods for eukaryotes: 16S rRNA chloroplast analysis, 18S rRNA sequencing, photosynthetic pigment analysis and microscopy. Consistent with our hypothesis, chloride and total nitrogen concentrations were among the most important statistical factors explaining the differences in taxonomic composition. These factors were positively correlated with the abundance of cryptophytes, haptophytes, and cyanobacteria. Ice-cover was also a major structuring factor, with clear differences between the winter communities and those of the open-water period. Nitrifying and methane oxidizing bacteria were more abundant in winter, suggesting the importance of anaerobic sediment processes and release of reduced compounds into the ice-covered water columns. The four methods for eukaryotic analysis provided complementary information. The 18S rRNA observations were strongly influenced by the presence of ribosome-rich ciliates, but revealed a much higher degree of taxonomic richness and greater separation of lakes, seasonal changes and potential salinity effects than the other methods. In many cold temperate lakes and rivers, the use of road de-icing salts in their catchments during winter has resulted in a pronounced increase of major ion concentrations, especially of the main road salt constituents sodium and chloride . This saMost studies to assess salinization effects on freshwater biota have been done via short term (days) laboratory experiments, often at salt concentrations that are well above the usual levels of perturbation e.g., , or haveGiven the seasonal timing of salt contamination in cold temperate lakes, analysis of salinization effects requires special attention to the overwintering microbial community. There is increasing research interest in under-ice microbiomes in lakes, and observations to date show that lakes maintain active microbial assemblages throughout winter with prokaryotic and eukaryotic communities that differ from those in summer e.g., . The seaOur aim in the present study was to identify the impacts of freshwater salinization on lake microbiomes, including during the less studied ice-cover period. We hypothesized that road salt exposure causes taxonomic changes in microbiome composition, and acts in concert with other known structuring factors, notably trophic state, and seasonal forcing. To assess this hypothesis, we investigated microbial community structure along with physical and chemical variables throughout all seasons, in four boreal lakes that were chosen to encompass contrasting salinity perturbations and trophic regimes.We used four methods to analyze the community structure of the microbial eukaryotes: classic microscopy, pigment analysis by High Pressure Liquid Chromatography (HPLC), and high throughput amplicon sequencing, targeting the V4 region of 18S rRNA and additionally the 16S rRNA in chloroplasts. Sequencing of 16S rRNA amplicons was also applied to analyze the prokaryotic communities. These methods each have their own biases, strengths and weaknesses, and a secondary aim of our study was to compare these methods in evaluating taxonomic structure in the four lakes.The four lakes selected for this study  are located within a 40 km-radius of Quebec City, Canada, and span a range of morphometries, trophic states, mixing regimes and other environmental conditions, including a gradient of urbanization impacts . During Lake Saint-Charles (LSC) is a drinking water supply for Quebec City, with the drinking water intake located 11 km downstream on its outflow, the Saint-Charles River. The lake is located in an urban area and is close to a major road (Highway 73), but most of its watershed is forested , and is –1), mainly due to the input of NaCl road salt from the highway, with chloride concentrations often exceeding the chronic exposure criterion for the protection of aquatic life of 120 mg L–1 (Lake Clément (LCL) is a recreational lake that can only be accessed by residents. It is located near Lake Saint-Charles, but closer to Highway 73, under which its main tributary flows . Its sal0 mg L–1 . This la–1 in 1970 to 700 μS cm–1 in 2000, with a stabilization since that time in the range 650–800  is a recreational urban lake with public access, where motor boating and seaplane landings are permitted. It is close to a major four-lane road (Highway 40), and like Lake Clément, it has an elevated salinity as a result of road salt application. Its specific conductivity increased rapidly with the completion and full operation of the highway, from 255 μS cm 650–800 . The lakFinally, Lake Clair (LCR) is located in the Duchesnay nature reserve, and although it is in close proximity to urban areas and the other studied lakes , its watThe four lakes were sampled throughout the year between January and October 2017, except in April, when conditions were too precarious due to ice break-up, with 3 sampling dates in the under-ice period and 3–4 sampling dates in the open water period . Samples2SO4, 0.1% final concentration), then kept at 4°C until concentrations were determined by a colorimetric method after persulfate digestion. Samples for major ions, dissolved organic carbon (DOC) and colored dissolved organic carbon (CDOM) were filtered through Milli-Q water pre-rinsed cellulose acetate filters , then acidified  and kept at 4°C until analysis. Anion concentrations were measured by ion chromatography , major cations by atomic emission spectroscopy , and trace cations by mass spectroscopy . DOC was measured by combustion catalytic oxidation , and CDOM was quantified by absorption at 440 nm measured in a Varian Cary 100 dual beam spectrophotometer  and total phosphorus (TP) samples were acidified . The solution was then filtered into an HPLC vial using a PTFE 0.2 μm filter. During extraction and in the HPLC vial, headspaces were filled with argon to avoid oxidation.a, chlorophyll b, chlorophyll c2, chlorophyll c3, chlorophyllide a, crocoxanthin, diadinoxanthin, diatoxanthin, echinenone, fucoxanthin, lutein, lycopene, MgDVP, myxoxanthophyll, peridinin, pheophorbide a, pheophytin a, prasinoxanthin, violaxanthin and zeaxanthin. This calibration allowed the conversion from absorbance to concentration. For unidentified pigments with a PDA spectrum, the conversion factor of the known pigment with both the closest spectrum and retention time was used, while for those with concentrations that were too small to resolve the spectrum, β,β-carotene and chlorophyll a conversion factors were used for carotenoids and chlorophylls respectively. The pigments assigned to the groups “unknown chlorophylls” or “unknown carotenoids” had recognizable spectra, but they eluted apart from identified chlorophylls and carotenoids, and likely included degradation products.HPLC analyses were performed by injecting the filtrates (100 μL) into a Thermo Scientific system  fitted with a Hypersil Gold C8 HPLC column  at 25°C, with a C8 guard column. The pigments were eluted by a succession of polar and non-polar solvents as described in a, with molecular weights obtained from a were used for carotenoids and chlorophylls, respectively. For some analyses, pigments were pooled as total carotenoids (Tot Caro: sum of known and unknown carotenoids), total chlorophylls  and total chlorophyll a .The abundance of different pigments was compared in terms of molar ratios to chlorophyll lsei function of the limSolve package), was used for these calculations  and stored in the dark at 4°C until analysis. Microscopy samples were analyzed using the Utermöhl protocol as described in The microbial eukaryotes were identified at the lowest taxonomic resolution possible and separated into subgroups by morphology. Biovolumes were estimated from simple geometric forms  from phoSamples for molecular analysis were filtered through 0.2 μm Sterivex units (Millipore), which were immediately filled with RNAlater (Life Technologies) and frozen at −80°C until extraction. The RNA was extracted using the AllPrep DNA/RNA Mini Kit (Qiagen) and the Qiagen protocol modified as follows: RLT + β-ME was injected into the Sterivex units, which were then incubated at 37°C for 45 min. Lysozyme and proteinase k were then added in the units, and they were incubated at 65°C for 15 min. In the RNA purification phase, a DNA digestion step was added between Qiagen kit steps 8 and 9: 10 μL of DNAse (Qiagen RNase free DNase set) diluted in 55 μL RDD Buffer was added in the RNeasy spin columns and left for 15 min at room temperature. RNeasy spin columns were then rinsed with Buffer RW1 as in step 8. Extracted RNA was tested for DNA contamination by a PCR and then converted to cDNA with the High Capacity cDNA Reverse Transcription Kit (Applied Biosystems-Ambion). The transcription was carried out in 20 μL  with the following thermal cycle: 25°C for 10 min, 37°C for 120 min and 85°C for 5 min. The cDNA was stored at −80°C until further analysis.The cDNA was amplified using two sets of primers modified with Illumina adaptors: (1) 515F/806R as modified by Forward and reverse read pairs were merged using BBMerge v37.36 , and theThe 18S rRNA sequences identified as embryophytes, arthropods, rotifers and mitochondria were removed from further analysis. A separate analysis was made of chloroplast reads from the 16S rRNA data. When pertinent, unidentified OTUs were submitted to a BLAST search to the nr database of NCBI GenBank and identified to the closest match. All the nucleotide sequence data are available in the NCBI database under the project number PRJNA681583.metaMDS function of the vegan package  analysis, with the  v2.5-6, . The rol v2.5-6, . In the DESeq2 package . The first axis was correlated with alkalinity, conductivity, Ca, K, Na, and Cl , while the second axis was only weakly correlated with Fe and CDOM . In this ordination, the lakes remained distinct and separated throughout the year, and the alkalinity/salinity gradient on the first axis also persisted throughout the year.The four lakes differed greatly in their chemical properties. The 25 samples clustered into four water chemistry groups that separated according to lake , and the lowest concentrations of TN and TP were found in Lake Clair .The chemical variation between the sampled lakes was mainly due to the concentrations and relative proportions of Ca, Cl, and Na . The latad salts . As expeAll lakes exhibited similar year-round patterns of temperature with warmer water during the open-water period and the usual inverse stratification profiles (cold overlying warmer water) during the ice-cover period . A thermOxygen in the surface water was near saturation with the atmosphere throughout the year in all lakes, while in the bottom water, oxygen levels were often well below saturation (≈50%), including periods of anoxia during summer/autumn in Lake Saint-Augustin and Lake Clément .–1), with small increases in bottom water during the open-water period. Lake Saint-Charles conductivity was about 10-times greater than Lake Clair, and always around 50% greater in surface compared to bottom waters. Conversely, in Lake Clément and Lake Saint-Augustin, conductivity was always 2–4 times greater in the bottom water, consistent with these lakes being fed by denser, saltier runoff from the roads. Also, the conductivities of the two lakes were 3–13 times higher than in Lake Saint-Charles. In these three lakes, maximum conductivity was observed during the late summer period of lowest inflows and the winter period of road salt use.Salinity, as measured by specific conductivity, was the most variable parameter, whether by depth or among lakes . Lake Cl–1).For the chemical and the biological analyses, all water was sampled from the surface, and the sampled communities from the four lakes were therefore from similar temperature and oxygenation levels for any period of sample collection, but with large differences in conductivity among sites . The chlorophyll concentration was correlated with total phosphorus when all samples were considered, but when samples from different periods were analyzed separately, this relationship was only significant during the open-water period (R2 = 0.82).The five identification methods provided complementary information on the taxonomic composition of the microbial community. During the ice-cover period, there was a selection for smaller cells with a higher chlorophyll content than in the open-water period, and the overall cell abundance was lower . In bothPolynucleobacter, Sediminibacterium, Polaromonas, Rhodoferax, and Caulobacter , represented mainly by the classes Betaproteobacteria (24–47%) and Alphaproteobacteria (9–27%) . At the lobacter .Synura, Cryptomonas, and Florenciella , 77% were identified at the genus level, and 72% at the species level. Depending on the lake, communities were either dominated by chrysophytes (2–79%) or cryptophytes (2–44% and enciella .Stephanodiscus), cryptophytes (2–38%) and ciliates  and chrysophytes . The communities, based on the composition inferred by the ratio of 17 selected pigments, were dominated by chrysophytes (13–79%), dinoflagellates (0–62%), and cryptophytes . Some pigments were identified by comparison to the standards (19%) or related to them , while the rest had different spectra and retention times, and could not be identified. The most abundant pigments were chlorophyll s 6–46%, .Asterionella, Tabellaria, and Synedra) and chloroplast 16S rRNA  in half or more of the samples, while only 1 OTU affiliated with this group in one sample was identified by 18S rRNA . Despite these distinctions, most of the OTUs were shared between the ice-cover and the open-water periods (77%); of the OTUs found only during a given period, 5% were from the ice-cover period and 95% from the open-water period. Almost half of the OTUs (40%) were shared among all the lakes, with few found only in either low or high conductivity lakes . The Shannon diversity indices were around 4, and neither this metric nor evenness (around 0.75) of the bacterial communities showed an influence of period (ice-cover vs. open-water) or salinity .At the phylum level for the prokaryotes, there was no differentiation between lakes and periods  and lakes  indicated an effect of season , but not among lakes , but there was no difference in evenness. The diversity index was about two times lower when calculated from microscopy than from the chloroplast 16S rRNA or 18S rRNA. A notable proportion of species were shared between lakes (22%) and periods (40%). No species was unique to the lakes with the highest salinization, while 13% of the species were only found in the lowest salinization lakes. There were unique species observed in the open-water period (53%), while few were unique to the ice-cover period (7%).The microscopy-derived biovolume data showed significant differences between the two periods . The diversity was higher during the open-water period , while the evenness was higher during the ice-cover period . The majority of OTUs were shared between the two periods , while only a small proportion of the OTUs were shared among all lakes . Concerning the OTUs that were only found in one period, the majority were unique to the open-water . No OTU was unique to the lakes with the highest salinization, while 15% of the OTUs were only found in the lakes with the lower salinization.The photosynthetic eukaryotic community inferred from the chloroplast 16S rRNA sequences showed significant differences between periods and among the lakes , with only 17% of OTUs shared by all lakes. A small proportion of the OTUs were unique to the lakes with the higher salinization (3%), while 19% of the OTUs were found only in the lakes with the lower salinization. About half of the OTUs were shared between the two periods, while 13% were unique to the ice-cover period, and 40% were exclusive to the open-water. The 18S rRNA communities were more diverse  and more even  during the open-water period.The 18S rRNA analyses showed differences between the ice-cover and the open-water at the phylum, the genus, and the OTU levels  were further used to identify changes in the abundance of taxonomic groups in response to the salinization gradient and ice-cover vs. open-water periods; for the microbial eukaryotes, the results from the microscopy and chloroplast 16S rRNA were similar to those from 18S rRNA and are presented in Dinobryon sociale and Mesodinium sp. The other group of lakes was characterized by the increase in the abundance of dinoflagellates, the cryptophytes Plagioselmis and Cryptomonas, and the haptophyte Diacronema (n = 394) that discriminated between the ice-cover and open-water periods  and the highest (Lake Clément and Lake Saint-Augustin) urbanization levels . The lakacronema . A secon periods . The iceciliates . During ciliates .Chthoniobacter sp. and soil-related Bacteroidetes  in both the ice-cover and the open-water periods. The variables related to salinization, such as Cl concentration, were among the most explanatory statistical factors, along with total nitrogen (TN), independent of the period and the identification method. For the eukaryotes, all methods resulted in the identification of the same factors with similar proportions of the total variation, but the depiction of community composition and its associated changes differed by method.During both periods, the concentration of chloride, and the concentration of total nitrogen were the most important drivers of the taxonomic composition of the microbial communities, both prokaryotes and eukaryotes, with all methods. In the studied lakes, Cl concentration is a proxy for total salinity, which is mostly influenced by bedrock type and urbanization level, as well as by the related road salt use. It was also correlated with alkalinity, which has previously been observed in road salt contaminated freshwater and attributed to concrete pavement weathering and cation exchange . Sodium Synechococccus, but it was not detected in the present study  between the lowest and the highest ends of the freshwater range . For Bacnt study . Howeverltic Sea . The resltic Sea . Chrysopronments . The hap the sea . The cryf 20 ppt . Cryptopf 20 ppt , and to f 20 ppt . A freshCyclotella and Stephanodiscus, which were identified as constituents in the present study , chemical  and ecological (predator populations) changes that result in a markedly different environment than in the open-water period. The distinct communities observed in the present study between the ice-cover and the open-water periods, are likely a complex response to this combination of differences. In the Saint-Charles River, ice-cover was identified as a major driving factor of community composition for both prokaryotes  and eukaNitrospira and Nitrotoga were identified as more abundant during the ice-cover than the open-water period. These nitrifying bacteria are often found together in wastewater treatment plants, and Nitrotoga has been identified as a low-temperature adapted genus . Although the surface waters of the studied lakes were almost fully oxygenated during the ice-cover period, the bottom waters had oxygen saturation values around 50%, with likely much lower oxygen tensions and possible anoxia in the lake sediments that would liberate reduced substrates into the water column. In contrast, the open-water period was characterized by the presence of cyanobacteria such as the bloom-forming Microcystis and Dolichospermum, as well as Rabdoderma and many unclassified picocyanobacteria.The bacterial communities during the ice-cover period appeared to have distinctive biogeochemical functions. In the present study, ed genus . Their ged genus . AnotherChlamydomonas and Oophila. Chlamydomonas is frequently encountered during the ice-cover period, including in perennially ice covered systems  of prokaryotes was not influenced by season, but the alpha-diversity of eukaryotes was higher during open-water period with all methods. Along the same lines, there were more species/OTUs unique to the open-water period than to the ice-cover period, both for prokaryotes and microbial eukaryotes, as has been previously observed for prokaryotes . While tin situ activity than 16S or 18S rRNA genes  as a measure of ribosomal potential for protein synthesis and a more accurate guide to potential NA genes . While sNA genes , there cNA genes .Mesodinium identified in the present study by 18S rRNA and microscopy, are also capable of kleptoplastidy , followed by microscopy and 16S rRNA in chloroplasts. The higher diversity using 18S rRNA as compared to microscopy has been attributed to its better detection of rare species due to higher total counts , its detection of cryptic or rare species, and to factors linked to sequencing errors and OTU groupings . The detMicroscopy, HPLC pigments and molecular analysis with either chloroplast 16S rRNA or 18S rRNA each provide useful ways to identify the factors driving differences in the taxonomic composition of microbial communities among sites, sampling times or experimental treatments. It is unusual to apply all five methods in a single study, but previous studies have used pairs of methods to differentiate communities: fluorescence (pigments) and microscopy ; 18S rRNConsistent with our hypothesis, there was a statistical relationship between community structure and chloride concentrations, notably on the relative abundance of cryptophytes and haptophytes, suggesting an influence of salinization across our sampled gradient of lakewater conditions. Large differences in trophic status and other limnological properties were insufficient to blanket out this effect, implying that the salt-rich runoff from roadside snowmelt may cause a shift in lake microbiomes during ice-cover as well as open-water periods. The application of diverse methods in the present study underscored the large differences between under-ice and open-water microbial communities. The seasonal differences included the tendency of the under-ice communities to have smaller algal cells, greater pigmentation, and higher relative abundances of methanotrophs, nitrifiers, and cryptophytes than the open-water communities. These results attest to the importance of extending limnological studies to all seasons, including winter, to capture the full range of microbiome compositions, functions and responses to contaminant exposure.https://www.ncbi.nlm.nih.gov/, PRJNA681583.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: IBF formulated the research question and designed the sampling, with input from WFV. IBF conducted the field sampling and the laboratory and data analyses. WFV provided funding. CL provided the infrastructure for the molecular analyses and advised IBF on the bioinformatics analyses. IBF led the writing of the manuscript with input from all authors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Malnutrition is a major health issue among Bangladeshi under-five (U5) children. Children are malnourished if the calories and proteins they take through their diet are not sufficient for their growth and maintenance. The goal of the research was to use machine learning (ML) algorithms to detect the risk factors of malnutrition  as well as their prediction.This work utilized malnutrition data that was derived from Bangladesh Demographic and Health Survey which was conducted in 2014. The selected dataset consisted of 7079 children with 13 factors. The potential risks of malnutrition have been identified by logistic regression (LR). Moreover, 3 ML classifiers (support vector machine (SVM), random forest (RF), and LR) have been implemented for predicting malnutrition and the performance of these ML algorithms were assessed on the basis of accuracy.The average prevalence of stunted, wasted, and underweight was 35.4%, 15.4%, and 32.8%, respectively. It was noted that LR identified five risk factors for stunting and underweight, as well as four factors for wasting. Results illustrated that RF can be accurately classified as stunted, wasted, and underweight children and obtained the highest accuracy of 88.3% for stunted, 87.7% for wasted, and 85.7% for underweight.This research focused on the identification and prediction of major risk factors for stunting, wasting, and underweight using ML algorithms which will aid policymakers in reducing malnutrition among Bangladesh’s U5 children. Malnutrition is one of the most serious health and welfare issues in any developing country, including Bangladesh. Malnutrition is referred to a lack of, excess, or imbalance in an individual’s energy and/or nutrient intake . MalnutrIn the case of Bangladesh, malnutrition affects more than half the population . A totalChild malnutrition is a hot topic in the field of public health as well as epidemiology globally. There were lots of studies about U5 malnutrition around the world. In previous studies, they focused only on the identification of the risk factors of malnutrition using classical model like logistic regression –3, 11–21th nationwide DHS, covering the entire population. The list of enumeration areas (EA) of the 2011 census population was provided by the bureau of statistics (BBS). The samples of households of BDHS, 2014 were collected using two-stage stratified sampling. In the 1st stage, 600 EAs were chosen at random, proportional to their number, and only 30 households were chosen using systematic sampling. Approximately 18, 000 ever-married women (age: 15–49 years) were selected for an interview and 17,863 (99%) women were successfully interviewed [This work utilized malnutrition data that has been derived from BDHS, 2014 which was conducted in 2014 and freely available online. It was the 7This study was based on an analysis of existing public domain survey datasets that are freely available online with all identifier information removed. The survey was approved by the Ethics Committee in Bangladesh. The authors were granted permission to use the data for independent research purposes.In this work, we have considered three types of response variables as stunted, underweight, and wasted, which were measured based on height-for-age Z-score (HAZ), weight-for-height Z-score (WHZ), and weight-for-age Z-score (WAZ). Using WHO AnthroPlus , the Z-scores were determined on the basis of age, weight, and height . ChildreAll categorical data was expressed as number (%). The chi-square analysis was implemented to assess the relationship between various selected explanatory variables and malnutrition . If the explanatory variables were statistically significantly associated with malnutrition, these significant variables were fed to LR model. LR based model was implemented to determine the risk factors of malnutrition. The significant risk factors were selected on the basis of p-value (p<0.05). Then three well-known and popular ML algorithms which were available in literature as support vector machine (SVM) , logistiThe overview of ML-based study was depicted in There are various kernels in SVM. As a result, the kernel of SVM must be optimized. In this work, we implemented SVM with 4 kernels: linear, RBF, Poly-2, and sigmoid. We tuned the hyper-parameters of these kernels using grid search methods. We optimized the kernel based on accuracy and chose the kernel with the highest accuracy. It was observed that RBF kernel provided the highest accuracy of 88.1% for stunted, 86.0% for wasted, and 85.6% for underweight compared to other kernels see . That isAccuracy and AUC were used to evaluate the efficiency of ML algorithms. Since the BDHS dataset was categorical, it was a very tedious task to choose a predictive model that could be accurately classified with the highest accuracy and AUC. The comparison of the efficiency of ML algorithms is depicted in The AUC of the ML algorithms was presented in The goal of this research was to identify risk factors for malnutrition and predict it using ML algorithms. Previously, only two studies on ML-based prediction of malnutrition status were conducted in Bangladesh, but they had lower accuracy , 24. In Male children historically provided more parental attention. This has recently changed. The government of Bangladesh has adopted some polices, including stipends and free education to improve female education. Our findings also revealed that the children whose father’s had no education, only primary and secondary education, were at a higher risk of being wasted and underweight than children whose father had a higher education . This stMany researches have been conducted on U5 malnutrition around the world. Among these few studies, there were two studies performed on stunted, wasted, and underweight , 24 and The main strength of this work is to extract high-risk factors of stunted, wasted, and underweight using a logistic regression model and make a decision based on the p-value. We used three ML algorithms  to predict stunted, wasted, and underweight children. Among them, RF-based classifier outperformed comparison to previous studies published in the literature. This work has some limitations. This work was only conducted on BHDS, 2014 cross-sectional data and no any post hoc analysis like Bonferroni correction was performed. In the future, we would like to consider pooled data as well as more factors to get precise results. We will also use principal component analysis, Fisher discriminant analysis, and mutual information for feature extraction of stunted, wasted, and underweight. We also attempt to use more ML algorithms in conjunction with deep learning classifiers and compare their results to this current work.Malnutrition is one of the most serious health and welfare issues in Bangladesh. The prevalence and risk factors of stunted, wasted, and underweight were investigated in this work and their status predicted using ML algorithms. LR results illustrated that five factors  were statistically significant for stunted and underweight, while four factors  for wasted. Results also indicated that RF classifier obtained the highest accuracy of 88.3% for stunted, 87.7% for wasted and 85.73% for underweight. This work suggests that LR-RF based combination may be accurately classified and predict stunted, wasted, and underweight and yield higher accuracy.


PSS and PSQI were correlated . The odds of high-stress were higher among those with poor sleep quality , low income , and no health insurance . Overall, in African-born Blacks living in America, daily life stress appears to be linked to poor quality sleep and exacerbated by low income and lack of health insurance.To identify determinants of daily life stress in Africans in America, 156 African-born Blacks (Age: 40 ± 10 years (mean ± SD), range 22–65 years) who came to the United States as adults (age ≥ 18 years) were asked about stress, sleep, behavior and socioeconomic status. Daily life stress and sleep quality were assessed with the Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index (PSQI), respectively. High-stress was defined by the threshold of the upper quartile of population distribution of PSS (≥16) and low-stress as PSS < 16. Poor sleep quality required PSQI > 5. Low income was defined as <40 k yearly. In the high and low-stress groups, PSS were: 21 ± 4 versus 9 ± 4,  African-born Blacks who migrate to the United States as adults are faced with the stress of changing countries, cultures, and continents ,2,3. StrBetween 2000 and 2016, the Black African immigrant population in the United States more than doubled from 574,000 to 1.6 million ,9.Stress both promotes and exacerbates cardiometabolic disease . PopulatOne aspect of stress is the challenge of coping with daily life, and another is long term stress such as living with the memory and consequences of adverse events which occurred over a lifetime ,5. The PReasons for African-born Blacks moving to the United States include seeking asylum/refugee status, work, study, family reunification, and the diversity visa program . IndepenThe INTER-HEART study is a global case-control study of risk factors for myocardial infarction . InitiatSleep quality and perceived stress are intertwined ,16. The To our knowledge PSS and PSQI have not been administered simultaneously in other African immigrant cohorts such as the Afro-Cardiac Study , the AfrTo understand daily life stress and sleep quality in African immigrants, PSS and PSQI were administered to 156 African-born Blacks who came to the United States as adults (age ≥ 18 years).ClinicalTrials.gov Identifier: NCT00001853). Written informed consent was obtained from every participant.The Africans in America cohort was established to assess both the well-being and cardiometabolic health of African-born Blacks living in the United States ,26,27,28Qualification for enrollment was determined by a telephone interview. Potential participants had to be born in a sub-Saharan African country and be between the ages of 18 and 70 years, currently live in the metropolitan Washington DC area, identify as Black, and report that both parents identified as Black and were also born in a sub-Saharan African country. Persons with a previous diagnosis of diabetes were excluded.Between 2016 and 2021, 218 consecutively enrolled African-born Blacks participated in two outpatient visits conducted at the NIH Clinical Center, Bethesda, Maryland .At Visit 1, social and medical histories were taken, and a physical examination, an electrocardiogram and routine blood tests were performed. Thirty-two participants were excluded because they were childhood immigrants, meaning their age at United States entry was <18 years. Childhood arrivals face different educational financial and acculturation pressures than adult arrivals . TherefoAt Visit 2, PSS and PSQI were administered. Weight, height, blood pressure (BP), waist circumference (WC), hemoglobin A1C and hemoglobin electrophoresis were obtained. In addition, oral glucose tolerance tests (OGTT)  were performed.Perceived stress was measured using the 10-question version of the PSS  4,5]. E,5. E4,5]The PSQI assesses sleep quality over the past month . The PSQSocio-economic variables were dichotomized and defined as education according to yes or no answers for college graduation, health insurance and partnered. Partnered was defined as married or living with significant other or not partnered  . Low incBehavioral variables included: smoking (yes or no in the last year), alcohol intake (one or more drinks per week vs. less than once per week) and physical activity. Physical activity was determined by the International Physical Activity Questionnaire (IPAQ) categories and dichotomized as sedentary (IPAQ category Low) versus active (IPAQ category Moderate and High combined) .Migration related issues included reason for moving to the United States, age at United States entry, and duration of residence in the United States (<10 years) ,23,30. HHemoglobin and hematocrit were measured in EDTA-anticoagulated whole blood using a Sysmex XE-5000. A1C levels were determined by HPLC using the National Glycohemoglobin Standardization Program (NGSP). Hemoglobin electrophoresis was performed with a Helena Zip-Zone electrophoresis instrument .t-tests. Categorical variables in both tables were compared by chi-square and Dunn tests, as appropriate.Unless stated otherwise, data are presented as mean ± SD. For the analyses of the three African regions of origin , continuHigh-stress was defined by the upper quartile of the population distribution for PSS. Then we performed a backward stepwise logistic regression to determine the association of 10 a priori social variables with the high-stress group. The 10 social variables were: poor sleep quality (PSQI > 5), income < 40 K, health insurance, life partner status, alcohol intake, education, reason for immigration, sedentary behavior, gender, and duration of United States residence . As the Poor sleep quality was defined by Buysse et al.  as PSQI p-values ≤ 0.05 were considered significant. Data were managed with Research Electronic Data Capture (REDCap) [(REDCap) . Analyse2, range 19.3 to 39.5 kg/m2) were mainly from countries in West (37%), Central (14%) and East (49%) Africa  Africa . The fouComparison by African region of origin revealed that BMI was highest in West Africans and income lowest in Central Africans. These differences by BMI and income are also true in sub-Saharan Africa . For thep < 0.001)  .p < 0.001). Having no life partner was also more common in the high-stress group than the low-stress group (p = 0.016), but academic achievement as measured by college graduation rate did not differ by group (p = 0.380).In addition, income was lower and health insurance coverage less frequent in the high-stress group (both p = 0.012)  . Howeverp = 0.160) but the difference did not achieve significance. However, the percentage of individuals who lived in the United States < 10 years tended to be higher in the high-stress than the low-stress group .For migration related variables, neither age at United States entry nor reason for immigration to the United States were different in the high-stress versus the low-stress group . The totp < 0.001).In a separate analysis the cohort was stratified by United States residence < 10 years or ≥10 years. The percent of individuals with income < 40 k was higher in the group with <10 years residence than ≥10 years .By backward stepwise logistic regression, the odds of being in the high-stress group were calculated for 10 social variables . The sigow at 5%  that no p < 0.001). Next, we determined which of the seven components of PSQI had the greatest influence on PSS. With PSS as the dependent variable and the seven components of the PSQI as independent variables (adjR2 = 32%), multiple linear regression revealed that three of the seven components of the PSQI had significantly influenced PSS. They were sleep disturbance (p < 0.001), daytime dysfunction (p < 0.001) and subjective sleep quality (p = 0.002) (p = 0.078).The Pearson correlation coefficient of PSS and PSQI was highly significant  . In addip < 0.001) and that their self-reported health was worse in the United States than in Africa (p < 0.001).In additional analyses regarding sleep, the participants reported that the number of hours slept in the United States were less than in Africa . Having sufficient finances to meet immediate needs such as paying for food and housing is a paramount challenge of life in the United States. But, beyond food and housing, there are two other forms of financial pressure which Africans in America enrollees experience: (a) the cost of health insurance; and (b) sending remittances to African relatives.Independent of race/ethnicity and nativity, lack of health insurance in the United States is a major source of anxiety. The lack of health insurance is often a proxy for low income , but in Adding to the economic pressure experienced by immigrants is the frequency with which money is sent back to families living in Africa . Currentp < 0.001). As longer duration of stay in the United States was associated with a higher income, longer duration of residence in the United States could be viewed as beneficial. However, studies which focused on cardiometabolic health have reported that residence in the United States for ≥10 years is associated with more hypertension, diabetes, and heart disease than United States residence < 10 years [Another challenge relative to income pertains to the duration of United States residence. The percent of individuals with income < 40 k was higher in the group with <10 years residence than >10 years , but an odds ratio was not calculated for having no life partner, because in the logistic regression for high-stress group membership the P-value for no life partner did not reach significance (p = 0.070)  .p < 0.001) and the odds of being stressed were increased if PSQI > 5 .The relationship between sleep quality and stress is known to be bidirectional, which means that each magnifies the adverse effect and consequences of the other ,16,37. Cp < 0.01). In addition, the effect of sleep duration on stress approached significance (p = 0.078).To gain insight into which of the seven components of the PSQI contributed most to perceived stress in African immigrants, we used the PSS score as the outcome variable and the seven components of PSQI as the independent variables. Three of the seven PSQI components increased the PSS score, specifically sleep disturbances, daytime dysfunction, and poor sleep quality . These findings reinforce the concept that smoking paradoxically increases stress even as it is simultaneously used as a coping strategy to decrease stress [In the Africans in America cohort, 5% of participants reported that they were smokers. A similarly low prevalence of smoking has been reported in both RODAM and the Afro-Cardiac cohorts ,41. Despe stress ,43.Precipitants of chronic stress are different from the factors which trigger daily life stress as measured by the PSS ,5. In prCohen and Williamson state that the reliability of PSS as a predictive tool of stress rapidly declines at four to eight weeks . TherefoFour factors which did not affect being in the high-stress group were: education, gender, exercise, and alcohol intake. The consensus is that higher education should be associated with higher income ,5. Even Women in the United States appear to experience more stress than men ,5,44,45.In the Africans in America cohort, sedentary behavior occurred in 22% of the cohort and did not differ by stress group. Importantly, the prevalence of sedentary behavior is 21% in sub-Saharan Africa and 23% in Ghanaian migrants to Europe ,47. The Alcohol intake did not vary by stress group. However, alcohol intake was evaluated as a dichotomous variable, specifically any alcohol intake versus no alcohol intake. Notably, Cohen et al. found that, when drinking was dichotomized between no drinking and drinking, no relationship between alcohol intake and PSS was detected ,5. HowevFrom two perspectives, data from the Africans in America cohort can be used to support the use of PSS and PSQI in African immigrants. First, the PSS was designed to detect daily life stress and not stress related to global life events. In the Africans in America cohort, with PSS as the outcome variable, low income, a daily life stressor, significantly affected PSS, but reason for immigration, a chronic stressor did not. Second, and as found in other populations, PSS and PSQI were highly correlated ,37,48,49Limitations of our study include the cross-sectional design, the use of a convenience sample and the relatively small sample size. However, our recruitment area includes not only metropolitan Washington, DC but also Montgomery County, MD and Prince George’s County, MD. All three of the areas are cited among the places in the United States with the highest concentrations of African-born Blacks . FurtherAnother weakness which can be addressed in future investigations is that neither perceived discrimination nor resilience were assessed in this investigation. This is important because discrimination occurs in daily life and profoundly influences both daily life stress and sleep quality . FurtherBoth daily life stress and sleep quality as assessed by PSS and PSQI provide important insight into the experience of African immigrants. Economic pressure and sleep quality are two factors which adversely affect daily stress and are potentially modifiable. Therefore, policy makers should consider providing services to immigrants which include financial counseling and information on sleep hygiene. Primary care providers along with clinical researchers should work to optimize the health and well-being of African immigrants by collecting data to assess daily life stress and sleep quality as well as perceived discrimination, resilience, and chronic stress.