Robust Output Feedback Control of Single-Link Flexible-Joint Robot Manipulator with Matched Disturbances Using High Gain Observer.

This article focuses on the output feedback control of single-link flexible-joint robot manipulators (SFJRMs) with matched disturbances and parametric uncertainties. Formally, four sensing elements are required to design the controller for single-link manipulators. We have designed a robust control technique for the semiglobal stabilization problem of the angular position of the link in the SFJRM system, with the availability of only a position sensing device. The sliding mode control (SMC) based output feedback controller is devised for SFJRM dynamics. The nonlinear model of SFJRM is considered to estimate the unknown states utilizing the high-gain observer (HGO). It is shown that the output under SMC using HGO-based estimated states coincides with that using original states when the gains of HGO are sufficiently high. Finally, the results are presented showing that the designed control technique works well when the SFJRM model is uncertain and matched perturbations are expected.

Respiratory syncytial virus G protein CX3C motif impairs human airway epithelial and immune cell responses.

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory infection in infants and young children and causes disease in the elderly and persons with compromised cardiac, pulmonary, or immune systems. Despite the high morbidity rates of RSV infection, no highly effective treatment or vaccine is yet available. The RSV G protein is an important contributor to the disease process. A conserved CX3C chemokine-like motif in G likely contributes to the pathogenesis of disease. Through this motif, G protein binds to CX3CR1 present on various immune cells and affects immune responses to RSV, as has been shown in the mouse model of RSV infection. However, very little is known of the role of RSV CX3C-CX3CR1 interactions in human disease. In this study, we use an in vitro model of human RSV infection comprised of human peripheral blood mononuclear cells (PBMCs) separated by a permeable membrane from human airway epithelial cells (A549) infected with RSV with either an intact CX3C motif (CX3C) or a mutated motif (CX4C). We show that the CX4C virus induces higher levels of type I/III interferon (IFN) in A549 cells, increased IFN-α and tumor necrosis factor alpha (TNF-α) production by human plasmacytoid dendritic cells (pDCs) and monocytes, and increased IFN-γ production in effector/memory T cell subpopulations. Treatment of CX3C virus-infected cells with the F(ab')2 form of an anti-G monoclonal antibody (MAb) that blocks binding to CX3CR1 gave results similar to those with the CX4C virus. Our data suggest that the RSV G protein CX3C motif impairs innate and adaptive human immune responses and may be important to vaccine and antiviral drug development.

Focal Hepatocellular Carcinoma in Pancreas.

A 67-year-old man was found to have a pancreatic head mass on abdominal ultrasound. He had compensated liver cirrhosis due to hepatitis C. The fine-needle aspiration (FNA) biopsy of the mass reported an adenocarcinoma of the pancreas, while the subsequent histopathology report of the supraclavicular lymph node showed features of hepatocellular carcinoma (HCC). A second read and additional stains on the FNA specimen confirmed a hepatoid (hepatocellular) carcinoma of the pancreas. He received atezolizumab and bevacizumab and had a good response. Tumors with features of HCC outside of the liver rarely occur and even more rarely in pancreas, with less than 50 cases reported so far. Pure HCC-like morphology is the most common histological form among four subtypes and has a relatively better prognosis. Surgical resection is considered the treatment of choice if amenable and variable outcomes are reported with different chemotherapies. Challenges exist in the diagnosis and the management of this rare and intriguing entity, and the potential misdiagnosis can have grave consequences as the management is completely different for a pancreatic adenocarcinoma and hepatoid carcinoma. We report a case with a challenging diagnosis of metastatic pancreatic hepatoid carcinoma which was treated as unresectable HCC with immunotherapy and the patient had a good response.

Post-Spinal Anesthesia Intradural Extramedullary Arachnoid Cyst Formation: A Case Report.

The formation of an intradural extramedullary arachnoid cyst is a rare complication of spinal anesthesia. We present a case of a 34-year-old female patient who developed neurological symptoms including a bilateral reduction in sensation and strength in the lower limbs following a C-section under spinal anesthesia. MRI of the thoracic spine revealed a lesion at the level of T11/T12 and the upper limit of the L1 vertebral body, which was pushing the cord to the side, and a diagnosis of the intradural extramedullary arachnoid cyst was established. The prognosis for this condition is good and surgical excision leads to resolution of the symptoms. Proper and prompt diagnosis is crucial to rule out other differentials and prevent permanent neurological damage in these patients.

A Rare Case of Paxlovid-Induced Pancreatitis.

Acute pancreatitis can result secondary to an inflammatory cascade due to an insult to the pancreatic parenchyma, whether it be from infections, medications, etc. We present a case of a 37-year-old male with acute pancreatitis after being started on Paxlovid, a combination drug containing Nirmatrelvir and Ritonavir, for COVID-19 treatment. Multiple reports in the literature have documented such an association between acute pancreatitis and the protease inhibitor Ritonavir. We suspect that similar results may have taken place that link the initiation of this medication with pancreatic inflammation.

Prevalence and Impact of Gastrointestinal Manifestations in COVID-19 Patients: A Systematic Review.

Background and objective: The aim of this study is to systematically analyze and summarize the implications of COVID-19 on the digestive system by quantitatively evaluating the prevalence of gastrointestinal symptoms such as nausea, vomiting, abdominal pain, constipation, diarrhea, anorexia. reported in COVID-19 cases. We simultaneously investigated other variables to determine the association of such symptoms in COVID-19 patients which can potentially influence the disease prognosis and outcome. This systematic review presents an updated literature on the issue as it requires more scientific discussion in order to better inform the medical community and authorities so that appropriate measures can be taken to control the virus outbreak. Methods: MEDLINE database was searched to identify relevant articles. Data was analyzed and synthesized from the 16 eligible studies which exclusively reported GI symptoms in COVID-19 patients along with the disease prognosis. A meta-analysis of studies having adequate information regarding the prevalence of specific GI symptoms in association with other relevant independent variables was performed. Results: From the search strategy, we identified 16 articles which fit our eligibility criteria comprising of 10 cross-sectional studies, 2 cohort study, 1 RCT and 3 observational studies. From these pooled studies, 6 articles exclusively talked about COVID-19 patients in which GI symptoms were reported and adequately discussed. In a total of 3646 patients, GI symptoms were documented in (16.2%-10.1%) patients. The most prevalent GI symptom was diarrhea (47%) but the most common clinical manifestation reported was fever (77.4%). Among the adult patients, hypertension (11.6%) was the most frequently reported comorbidity. Presence of viral RNA in stool sample was noted in 16.7% patients with GI symptom. In patients who complained of having GI symptoms, an abnormal liver function was largely observed, with an elevated ALT level in (10.9%) and an elevated AST in (8.8%) of the patients. Evidence of vertical transmission (14.2%) was reported in one study which highlights the extent and mode of viral transmission. It was observed that a great majority of the patients in the 6 studies reporting specifically on patients with GI symptoms were on antiviral therapy (68.6%) as the standard disease management protocol but the eventual disease outcome as in this case died (8.4%), discharged (45.6%) was not linked to just one therapeutic factor but other indicators of disease severity such as positive chest CT findings (87.82%) have led to a poor disease prognosis which was noted in (28.9%) severe patients with GI symptoms compared to (71.1%) non-severe COVID-19 patients with GI symptom. Conclusion: Presence of GI symptoms in COVID-19 patients has shown to have a positive association with the poor disease prognosis likely as a result of direct viral toxicity. It is important for the physicians to recognize digestive symptoms as an important characteristic in COVID-19 patients. Hence, precise and targeted documentation of GI symptoms and viral stool sample investigations should be performed in order to understand the rapidly evolving disease symptomology.

Carbon monoxide: raising awareness of the silent killer in the emergency department.

BACKGROUND: Carbon monoxide (CO) is an odourless gas produced by the incomplete combustion of carbon containing materials. CO poisoning causes a range of symptoms of which headache is the most common, occurring in up to 90% of patients. An audit in the Emergency Department at University Hospital Aintree, Liverpool, UK found a lack of clinical awareness among healthcare professionals (HCPs) with CO exposure being considered in only 0.8% of patients presenting with non-traumatic headache. This Quality Improvement Project (QIP) aimed to increase this consideration to 50% of presentations. METHODS: Three separate sequential Plan Do Study Act (PDSA) cycles were instigated. Interventions involved verbal reminders to frontline HCPs (cycle 1), using strategically placed CO posters (cycle 2) and finally designing and introducing a CO sticker education scheme (cycle 3). These stickers, highlighting the approved CO COMA acronym, were placed in patient notes to serve as a physical reminder for HCPs when seeing patients. Rapid cycle sequencing was used with each cycle lasting 2 weeks. Patient notes were analysed for evidence that the HCP considered a diagnosis of CO. RESULTS: An average of 61 patients were included in each PDSA cycle. Given baseline findings, each cycle demonstrated positive results with CO awareness being considered in 1.7% and 10.0% of patients with non-traumatic headache following cycles 1 and 2, respectively. The final PDSA cycle demonstrated significant increase in consideration of CO to 42.1% of non-traumatic headache presentations. CONCLUSION: This QIP demonstrated that even small interventions can lead to significant change in awareness of CO exposure. Implementation of a CO sticker education scheme is a feasible way of increasing awareness among emergency care professionals and serves as a low-cost, easy to use, transferable and sustainable solution to address the lack of CO awareness in acute emergency settings. Importantly, this serves to promote improved patient safety.

Esophagitis Dissecans Superficialis: A Frequently Missed and Rarely Reported Diagnosis.

Esophagitis dissecans superficialis (EDS) is a rare esophageal disease with a wide spectrum of presentations from asymptomatic to debilitating symptoms. There is a strong association of EDS with autoimmune diseases, smoking, and medications, but it can also be idiopathic. Due to the sporadic occurrence of EDS, identification requires a high index of suspicion to avoid frequent misdiagnoses. Herein, we present a case of EDS associated with the long-standing use of oral diclofenac with a favorable outcome after therapy with a proton pump inhibitor (PPI).

Gastrointestinal Hemorrhage Due to Duodenal Varix: A Case Report.

We report a case of a 72-year-old female with a past medical condition of non-alcoholic steatohepatitis who presented in the emergency department with altered mentation. An Esophagogastroduodenoscopy was performed which showed a normal esophagus and stomach, but revealed grade III varices which were appreciable in the second portion of the duodenum. Her colonoscopy report revealed multiple small and large mouthed diverticula in the sigmoid colon along with hematin throughout the colon, yet no evidence of active bleeding, mass or inflammation. We discuss the patient's rarity of the clinical entity, clinical development, and elements used for diagnosis along with the treatment modalities involved.

Clinical Implementation and Initial Experience of Neutrophil Gelatinase-Associated Lipocalin Testing for the Diagnostic and Prognostic Assessment of Acute Kidney Injury Events in Hospitalized Patients.

INTRODUCTION: The use of novel kidney injury biomarkers has been shown to improve diagnostic assessment and prognostic prediction in various populations with acute kidney injury (AKI), but their use in a standard clinical practice have been rarely reported. METHODS: We reported the clinical implementation of neutrophil gelatinase-associated lipocalin (NGAL) measurement for routine AKI diagnostic workup of patients receiving nephrology consultation in a tertiary academic centre. Specific focus was made on the diagnostic performance to discriminate functional ("pre-renal") from intra-renal AKI and to predict AKI progression. RESULTS: Forty-five urine NGAL (uNGAL) and 25 plasma NGAL (pNGAL) samples in the first 50 consecutive patients were analysed. KDIGO Stage 1, 2, 3 AKI, and renal replacement therapy occurred in 10%, 40%, 50%, and 24% of cases, respectively. The uNGAL was lower in patients with transient AKI (<48 h) and no sign of urinary tract infections (37 [25-167] ng/mL) than sustained or progressive AKI (298 [74-1,308] ng/mL) (p = 0.016), while pNGAL did not discriminate transient (264 [100-373] ng/mL) from persistent AKI (415 [220-816] ng/mL) (p = 0.137). The median uNGAL level was 63 (35-1,123) ng/mL for functional/pre-renal AKI and 451 (177-1,315) ng/mL for intra-renal AKI (p = 0.043), while the pNGAL was 264 (114-468) and 415 (230-816) ng/mL (p = 0.235), respectively. CONCLUSION: NGAL, as part of the routine workup, is useful for diagnostic and prognostic assessment of new-onset AKI in clinical practice. Interpretation of an increased NGAL level should be clinically evaluated in its clinical context, particularly considering concomitant infection (urinary or systemic). Clinical adoption of emerging AKI biomarkers as diagnostic tests in clinical practice should be further encouraged.

High-gain observer-based nonlinear control scheme for biomechanical sit to stand movement in the presence of sensory feedback delays.

Sit-to-stand movement (STS) is a mundane activity, controlled by the central-nervous-system (CNS) via a complex neurophysiological mechanism that involves coordination of limbs for successful execution. Detailed analysis and accurate simulations of STS task have significant importance in clinical intervention, rehabilitation process, and better design for assistive devices. The CNS controls STS motion by taking inputs from proprioceptors. These input signals suffer delay in transmission to CNS making movement control and coordination more complex which may lead to larger body exertion or instability. This paper deals with the problem of STS movement execution in the presence of proprioceptive feedback delays in joint position and velocity. We present a high-gain observer (HGO) based feedback linearization control technique to mimic the CNS in controlling the STS transfer. The HGO estimates immeasurable delayed states to generate input signals for feedback. The feedback linearization output control law generates the passive torques at joints to execute the STS movement. The H2 dynamic controller calculates the optimal linear gains by using physiological variables. The whole scheme is simulated in MATLAB/Simulink. The simulations illustrate physiologically improved results. The ankle, knee, and hip joint position profiles show a high correlation of 0.91, 0.97, 0.80 with the experimentally generated reference profiles. The faster observer dynamics and global boundness of controller result in compensation of delays. The low error and high correlation of simulation results demonstrate (1) the reliability and effectiveness of the proposed scheme for customization of human models and (2) highlight the fact that for detailed analysis and accurate simulations of STS movement the modeling scheme must consider nonlinearities of the system.

Dieulafoy lesions as cause of upper gastrointestinal bleeding in a patient with portal hypertension.

Dieulafoy's lesion is an abnormally large and tortuous submucosal artery that protrudes through a small mucosal defect resulting in gastrointestinal bleeding. We present a case of a 53-year-old man with a history of HIV and alcohol abuse who presented to the emergency room with hematemesis and melena. Upper endoscopy revealed an actively bleeding dieulafoy lesion, but due to uncontrolled bleeding, embolization of the left artery was necessitated. The incidence of dieulafoy lesions is about 0.3% to 6.7% within the stomach. The etiology remains uncertain but has been linked to alcoholism and antiplatelet drugs. We are emphasizing the importance of considering uncommon causes of upper gastrointestinal bleeding in patients with portal hypertension.

Colovesicular fistula from Candida dubliniensis in an immunocompetent resulting in poor outcome.

is a rare fungal opportunistic infection originally isolated from the oral cavity of severely immunocompromised individuals. We present a case of a candidiasis infection in a patient with only decompensated liver cirrhosis and diabetes mellitus as his immunocompromising risk factors, resulting in severe fungemia and death within 5 days despite being on antifungal therapy.

Investigating the awareness level about diabetes mellitus and associated factors in Tarlai (rural Islamabad).

OBJECTIVES: To determine the baseline level of awareness amongst a rural community about Diabetes Mellitus (irrespective of type 1 or type 2), its risk factors and complications. METHODS: This was a cross-sectional survey conducted at the community of Tarlai, Islamabad, Pakistan, in January of 2008. A structured questionnaire was used and 300 adults (age > or = 18 years) were assessed on their knowledge regarding awareness of Diabetes Mellitus, its risk factors and complications. All data collected was entered into SPSS version 10.0. The data was re-validated and analyzed. RESULTS: Out of the three hundred adults subjected to the survey, only 129 (43%) adults had any awareness of Diabetes Mellitus. Adults with no regular, scheduled exercise were 221 (73.7%) and 256 (85.3%) did not have healthy eating habits. Awareness of risk factors was present in 42 (14%) while awareness of the complications associated with the disease was 65 (22%). Adults which reported as never going for regular checkups to any clinic or hospital were 232 (77%). Family history of diabetes mellitus was statistically significantly associated with awareness about diabetes mellitus (65% vs 32%, p < 0.001), people who were in contact regularly with health care providers were more aware about diabetes and the associated risk factors than those who were not (71% vs 35%, p < 0.001). Sex was not associated (p = 0.28) with awareness about diabetes mellitus, nor was the educational status (p = 0.46). CONCLUSIONS: Majority of adults were unaware of Diabetes Mellitus itself and associated risk factors. Raising public awareness of the disease through outreach programmes and mass media should be planned and implemented.

Case report and literature review of auto-brewery syndrome: probably an underdiagnosed medical condition.

Auto-brewery syndrome (ABS), also known as gut fermentation syndrome, is a rarely diagnosed medical condition in which the ingestion of carbohydrates results in endogenous alcohol production. The patient in this case report had fungal yeast forms in the upper small bowel and cecum, which likely fermented carbohydrates to alcohol. Treatment with antifungal agents allowed subsequent ingestion of carbohydrates without symptoms. He had been exposed to a prolonged course of antibiotics before this occurred. We postulate that the antibiotic altered his gut microbiome, allowing fungal growth. This diagnosis should be considered in any patient with positive manifestations of alcohol toxicity who denies alcohol ingestion. The aim of this case report was confirmation and treatment of ABS using a standardised carbohydrate challenge test followed by upper and lower endoscopy to obtain intestinal secretions to detect fungal growth. These fungi were speciated and antifungal sensitivity performed. This allowed the use of appropriate therapy. The patient was kept on a carbohydrate-free diet during the initial 6-week period of therapy. A single-strain probiotic for competitive inhibition of fungal growth was given to the patient. This probiotic was later replaced by a multistrain bacterial probiotic hoping that the multiple bacteria would inhibit fungi better than a single-strain. The beneficial role of probiotics in this condition has not been studied. The patient was rechallenged for endogenous alcohol production prior to reintroducing carbohydrates in his diet.

Burkitt Lymphoma of the Duodenum: An Uncommon Phenomenon.

Burkitt lymphoma is an aggressively growing tumor commonly found in African children, involving the jaw and facial bones. Most non-Hodgkin lymphoma tumors involve extra nodal sites like the nervous system and gastrointestinal tract. A rare variant of this type of lymphoma is found in immunocompromised patients specifically in the gastrointestinal tract with accompanying gastrointestinal symptoms. Burkitt lymphoma is a malignancy that has commonly presented in GI tract but rarely in the duodenum. This clinical variant can commonly involve stomach, ileum, and cecum. However, there is very limited data available regarding the duodenal growth of this tumor. Duodenal involvement of Burkitt lymphoma is extremely rare and accounts for < 1% of all lymphomas. We present a case report of an older patient with a duodenal Burkitt lymphoma diagnosed by biopsy. A high suspicion should be present while treating immunocompromised patients with chronic abdominal symptoms especially with complications such as bleeding or occult positive testing. Early endoscopy intervention with biopsy can help identity and treat these conditions with improved outcomes for the patients.

A Case of Auto-brewery Syndrome Treated with Micafungin.

Auto-brewery syndrome is caused by alcohol brewing inside the human body; it is a rare clinical condition where the patient becomes inebriated without exogenous alcohol use. Yeast is responsible, and treatment requires an appropriate antifungal agent. If undiagnosed, the patient's life becomes a misery. We present a case of a 45-year-old male who suffered from this condition for over three years with two arrests for driving under the influence prior to being diagnosed. The patient stated that he felt the episodes were related to his meal intakes; therefore, he would skip most meals of the day. The patient visited several centers where he was told there was not much they could offer him and he was left without a diagnosis. A carbohydrate challenge test in a monitored setting showed elevated blood alcohol levels. He was treated with antifungals and a low carbohydrate diet which resulted in the resolution of his symptoms. Hence the importance of awareness among physicians is necessary along with a high index of suspicion.

A case report of gastric emphysema induced by noninvasive positive airway pressure.

Gastric emphysema is a rare medical condition in which air penetrates any layer of the gastric wall (mucosa, submucosa, muscle layer, or serosa) due to a noninfectious source. It is essential to differentiate this from a life-threatening condition known as emphysematous gastritis. These two conditions have a similar presentation, and therefore, it is difficult to differentiate the two on imaging. Bi-level positive airway pressure (BiPAP) is a noninvasive intervention for selected patients in respiratory distress. This intervention uses positive airway pressure to prevent endotracheal intubation. The commonly noted side effects of positive airway pressure are dry mouth and oral irritation. This is the first case, to our knowledge, of gastric emphysema directly originating from BiPAP administration. It was diagnosed on imaging as pneumatosis intestinalis and emphysematous gastritis but clinical presentation was benign. The condition resolved immediately after discontinuation of BiPAP.

Unusual complication of a percutaneous gastrostomy tube.

Percutaneous Gastrostomy (PEG) tube is an endoscopic-guided procedure to provide enteral nutrition, medications and/or fluids to patients with oral or esophageal pathologies. PEG tubes are a relatively safe intervention but commonly known to have complications like insertion site infection, tube leakage, and tube blockage. This was an unusual case in which the PEG tube was discovered to be obstructing the third part of the duodenum after migration resulting in mechanical gastric obstruction with septic shock and severe hemodynamic instability. PEG induced gastric obstruction is often misdiagnosed during a triage due to the atypical presentation of this condition leading to aggressive management, testing and consultations. PEG dependent patients have rapidly increased over the years and a complete physical examination of the PEG site should be performed by all physicians in order to prevent related complications.

A rare case of metastatic small cell neuroendocrine carcinoma of the lung presenting as isolated thrombocytopenia.

Small cell neuroendocrine carcinoma (SNEC) is a high grade and poorly differentiated neuroendocrine tumor which typically presents as a primary pulmonary neoplasm near the bronchial region. Due to the aggressive nature of the tumor, there are many ways it can initially present, mostly involving the lungs. We present a case of a 68-year-old male patient who initially presented with new-onset of severe thrombocytopenia with superimposed pneumonia. It was late in the progression of the disease that histopathology from the bone marrow confirmed SNEC, which presented only after it metastasized to the bone marrow by way of a rare paraneoplastic syndrome. Furthermore, the bone marrow biopsy revealed atypical markers not commonly seen in SNEC. Since this was such an atypical presentation of SNEC, management was limited to stabilization of the patient. The patient expired two weeks later.