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Molecular Therapy. Methods & Clinical... Jun 2024Mucolipidosis IV (MLIV) is a rare, autosomal recessive, lysosomal disease characterized by intellectual disability, motor deficits, and progressive vision loss. Using...
Mucolipidosis IV (MLIV) is a rare, autosomal recessive, lysosomal disease characterized by intellectual disability, motor deficits, and progressive vision loss. Using adeno-associated vector 9 (AAV9) and AAV-PHP.B as delivery vectors, we previously demonstrated the feasibility of modifying disease course in a mouse model of MLIV by the human gene transfer. Here, using a primate-enabling capsid AAV.CPP.16 (CPP16), we constructed a new, clinic-oriented gene expression vector and demonstrated its efficacy in the preclinical model of MLIV. Systemic administration of CPP16-MCOLN1 in adult symptomatic mice at a dose of 1e12 vg per mouse resulted in expression in the brain and peripheral tissues, alleviated brain pathology, rescued neuromotor function, and completely prevented paralysis. Notable expression of transcripts was also detected in the retina of the mouse, which had exhibited significant degeneration at the time of the treatment. However, no increase in retinal thickness was observed after gene therapy treatment. Our results suggest a new AAV-based systemic gene replacement therapy for the treatment of MLIV that could be translated into clinical studies.
PubMed: 38934011
DOI: 10.1016/j.omtm.2024.101269 -
Neuro-ophthalmology (Aeolus Press) 2024Millard-Gubler syndrome is a pontine syndrome caused by a lesion in the lower pons region. It is characterised by ipsilateral facial paralysis and VI paresis and...
Millard-Gubler syndrome is a pontine syndrome caused by a lesion in the lower pons region. It is characterised by ipsilateral facial paralysis and VI paresis and contralateral brachiocrural palsy. We present the case of a female patient, G4P2A1, at 21 weeks of gestation, with preeclampsia, complaints of blurred vision, diplopia, and right hemiparesis, in whom a clinical diagnosis of Millard-Gubler syndrome was made. Neuroimaging showed an intraparenchymal haemorrhage towards the central portion of the bulbopontine junction. An extensive aetiological study was carried out to determine the cause of the hypertensive disorder syndrome during pregnancy. The patient improved satisfactorily from the neurological deficit after delivery of an early stillbirth.
PubMed: 38933747
DOI: 10.1080/01658107.2024.2303708 -
Clinical Case Reports Jul 2024Insertion of a nasogastric tube is one of the most common methods of administering nutrition, but can cause vocal cord paralysis.
Insertion of a nasogastric tube is one of the most common methods of administering nutrition, but can cause vocal cord paralysis.
PubMed: 38933707
DOI: 10.1002/ccr3.8960 -
Cureus May 2024The opioid-abuse epidemic is a problem that continues to persist world-wide. As such, appropriately evaluating and treating such patients is crucial, especially when...
The opioid-abuse epidemic is a problem that continues to persist world-wide. As such, appropriately evaluating and treating such patients is crucial, especially when considering the various complications that may arise. In rare cases, opioid overdoses can be complicated by compartment syndrome, rhabdomyolysis, and acute renal failure. All three of these complications can result in life threatening emergencies. We present a case of a 38-year-old male who was brought to the emergency department after reportedly being found lying on the ground for an unknown period of time from suspected heroin overdose. He was initially treated with 2 milligrams (mg) of intramuscular naloxone en route via emergency medical services with appropriate response. Shortly after arrival to the emergency department, the patient complained of severe right lower extremity pain, paresthesia and paralysis. Patient developed acute lower extremity compartment syndrome that was further complicated by rhabdomyolysis and acute renal failure. While emergency medicine physicians are familiar with the common complications of heroin overdose including mental status changes, respiratory depression and gastrointestinal symptoms, they must also be familiar with the less common ones. Notably, acute compartment syndrome. Compartment syndrome is ultimately a clinical diagnosis and warrants emergent surgical consultation. Every patient presenting to the emergency department warrants a complete, thorough physical examination to evaluate for any and all life-threatening conditions, regardless of the presenting complaint.
PubMed: 38933622
DOI: 10.7759/cureus.61144 -
Global Health Action Dec 2024The Global Polio Eradication Initiative (GPEI) helped develop the standard acute flaccid paralysis surveillance (AFP) system worldwide, including, knowledge, expertise,...
The evolution, facilitators, barriers, and additional activities of acute flaccid paralysis surveillance platform in polio eradication programme Bangladesh: a mixed-method study.
BACKGROUND
The Global Polio Eradication Initiative (GPEI) helped develop the standard acute flaccid paralysis surveillance (AFP) system worldwide, including, knowledge, expertise, technical assistance, and trained personnel. AFP surveillance can complement any disease surveillance system.
OBJECTIVE
This study outlines AFP surveillance evolution in Bangladesh, its success and challenging factors, and its potential to facilitate other health goals.
METHODS
This mixed-method study includes a grey literature review, survey, and key informant interviews (KIIs). We collected grey literature from online websites and paper documentation from GPEI stakeholders. Online and in-person surveys were conducted in six divisions of Bangladesh, including Dhaka, Rajshahi, Rangpur, Chittagong, Sylhet, and Khulna, to map tacit knowledge ideas, approaches, and experiences. We also conducted KIIs, and Data were then combined on focused emerging themes, including the history, challenges, and successes of AFP surveillance programme.
RESULTS
According to the grey literature review, survey, and KII, AFP surveillance successfully contributed to decreasing polio in Bangladesh. The major facilitating factors were multi-sectoral collaboration, Surveillance Immunization Medical Officer (SIMO) network activities, social environment, community-based surveillance, and promising political commitment. On the other hand, high population growth, hard-to-reach areas, people residing in risky zones, and polio transition planning were significant challenges. Bangladesh is also utilizing these polio surveillance assets for other vaccine-preventable diseases.
CONCLUSION
As the world is so close to eradicating polio, the knowledge, and other assets of the AFP surveillance, could be used for other health programmes. In addition, its strengths can be leveraged for combating new and emerging diseases.
Topics: Humans; Poliomyelitis; Bangladesh; Disease Eradication; Population Surveillance; Surveys and Questionnaires; Paralysis
PubMed: 38932666
DOI: 10.1080/16549716.2024.2370096 -
Sensors (Basel, Switzerland) Jun 2024For individuals with spinal cord injuries (SCIs) above the midthoracic level, a common complication is the partial or complete loss of trunk stability in the seated...
For individuals with spinal cord injuries (SCIs) above the midthoracic level, a common complication is the partial or complete loss of trunk stability in the seated position. Functional neuromuscular stimulation (FNS) can restore seated posture and other motor functions after paralysis by applying small electrical currents to the peripheral motor nerves. In particular, the Networked Neuroprosthesis (NNP) is a fully implanted, modular FNS system that is also capable of capturing information from embedded accelerometers for measuring trunk tilt for feedback control of stimulation. The NNP modules containing the accelerometers are located in the body based on surgical constraints. As such, their exact orientations are generally unknown and cannot be easily assessed. In this study, a method for estimating trunk tilt that employed the Gram-Schmidt method to reorient acceleration signals to the anatomical axes of the body was developed and deployed in individuals with SCI using the implanted NNP system. An anatomically realistic model of a human trunk and five accelerometer sensors was developed to verify the accuracy of the reorientation algorithm. Correlation coefficients and root mean square errors (RMSEs) were calculated to compare target trunk tilt estimates and tilt estimates derived from simulated accelerometer signals under a variety of conditions. Simulated trunk tilt estimates with correlation coefficients above 0.92 and RMSEs below 5° were achieved. The algorithm was then applied to accelerometer signals from implanted sensors installed in three NNP recipients. Error analysis was performed by comparing the correlation coefficients and RMSEs derived from trunk tilt estimates calculated from implanted sensor signals to those calculated via motion capture data, which served as the gold standard. NNP-derived trunk tilt estimates exhibited correlation coefficients between 0.80 and 0.95 and RMSEs below 13° for both pitch and roll in most cases. These findings suggest that the algorithm is effective at estimating trunk tilt with the implanted sensors of the NNP system, which implies that the method may be appropriate for extracting feedback signals for control systems for seated stability with NNP technology for individuals who have reduced control of their trunk due to paralysis.
Topics: Humans; Algorithms; Accelerometry; Torso; Spinal Cord Injuries; Neural Prostheses; Posture
PubMed: 38931600
DOI: 10.3390/s24123816 -
Microorganisms May 2024Biotic stress in cotton plants caused by the phytopathogenic fungus var. triggers symptoms of ramulosis, a disease characterized by necrotic spots on young leaves,...
Biotic stress in cotton plants caused by the phytopathogenic fungus var. triggers symptoms of ramulosis, a disease characterized by necrotic spots on young leaves, followed by death of the affected branch's apical meristem, plant growth paralysis, and stimulation of lateral bud production. Severe cases of ramulosis can cause up to 85% yield losses in cotton plantations. Currently, this disease is controlled exclusively by using fungicides. However, few studies have focused on biological alternatives for mitigating the effects of contamination by var. on cotton plants. Thus, the hypothesis raised is that endophytic fungi isolated from an Arecaceae species (), endemic to the Cerrado biome, have the potential to reduce physiological damage caused by ramulosis, decreasing its severity in these plants. This hypothesis was tested using plants grown from seeds contaminated with the pathogen and inoculated with strains of (BP10EF), (BP33EF), sp. (BP328EF), (BP335EF), and sp. (BP340EF). var. is a leaf pathogen; thus, the evaluations were focused on leaf parameters: gas exchange, chlorophyll a fluorescence, and oxidative metabolism. The hypothesis that inoculation with endophytic strains can mitigate physiological and photochemical damage caused by ramulosis in cotton was confirmed, as the fungi improved plant growth and stomatal index and density, increased net photosynthetic rate () and carboxylation efficiency (/), and decreased photochemical stress (ABS/RC and DI/RC) and oxidative stress by reducing enzyme activity (CAT, SOD, and APX) and the synthesis of malondialdehyde (MDA). Control plants developed leaves with a low adaxial stomatal index and density to reduce colonization of leaf tissues by var. due to the absence of fungal antagonism. The sp. strain BP328EF can efficiently inhibit var. in vitro (81.11% relative inhibition), improve gas exchange parameters, reduce photochemical stress of chlorophyll-, and decrease lipid peroxidation in attacked leaves. Thus, BP328EF should be further evaluated for its potential effect as a biological alternative for enhancing the resistance of plants and minimizing yield losses caused by var. .
PubMed: 38930506
DOI: 10.3390/microorganisms12061124 -
Microorganisms May 2024Verifying the inclusivity of molecular detection methods gives indications about the reliability of viral infection diagnosis because of the tendency of viral pathogens...
Verifying the inclusivity of molecular detection methods gives indications about the reliability of viral infection diagnosis because of the tendency of viral pathogens to undergo sequence variation. This study was aimed at selecting inclusive probes based on reverse transcription-quantitative PCR (RT-qPCR) assays for the diagnosis of the most widespread and detrimental viruses infecting honeybees, namely the acute bee paralysis virus (ABPV), the black queen cell virus (BQCV), the chronic paralysis bee virus (CBPV), the deformed wing virus variants A (DWVA) and B (DWVB), and the sacbrood virus (SBV). Therefore, previously described detection methods were re-evaluated in silico for their specificity and inclusivity. Based on this evaluation, selected methods were modified, or new ones were designed and tested in duplex RT-qPCR reactions. The limits of detection (LODs), effect of multiplexing on sensitivity and the viral RNA quantification potential in bees and hive debris were assessed. This study made available diagnostic assays able to detect an increased number of virus variants compared with previously described tests and two viral pathogens in a single PCR reaction.
PubMed: 38930487
DOI: 10.3390/microorganisms12061105 -
Medicina (Kaunas, Lithuania) May 2024: Changes in activities of daily living (ADL) and quality of life (QOL) of patients with bone metastasis who underwent surgical treatment through Bone Metastasis Cancer...
Evaluation of Changes in Activities of Daily Living and Quality of Life of Patients with Bone Metastasis Who Underwent Conservative Therapy through Bone Metastasis Cancer Boards.
: Changes in activities of daily living (ADL) and quality of life (QOL) of patients with bone metastasis who underwent surgical treatment through Bone Metastasis Cancer Boards (BMCBs), a recent multidisciplinary approach for managing bone metastases, have been reported; however, no reports exist on patients who undergo conservative treatment. In this study, we aimed to evaluate these patients' ADL and QOL and examine the factors influencing changes in these parameters. : We retrospectively reviewed 200 patients with bone metastases who underwent conservative therapy through BMCBs between 2013 and 2021. A reassessment was conducted within 2-8 weeks after the initial assessment. Patients' background and changes in performance status (PS), Barthel Index (BI), EuroQol five-dimension (EQ-5D) scores, and Numerical Rating Scale (NRS) scores were initially assessed. Furthermore, we categorized patients into two groups based on improvements or deteriorations in ADL and QOL and performed comparative analyses. : Significant improvements in EQ-5D (0.57 ± 0.02 versus [vs.] 0.64 ± 0.02), NRS max (5.21 ± 0.24 vs. 3.56 ± 0.21), and NRS average (2.98 ± 0.18 vs. 1.85 ± 0.13) scores were observed between the initial assessment and reassessment (all < 0.001). PS (1.84 ± 0.08 vs. 1.72 ± 0.08) and BI (83.15 ± 1.68 vs. 84.42 ± 1.73) also showed improvements ( = 0.06, and 0.054, respectively). In addition, spinal cord paralysis (odds ratio [OR]: 3.69, = 0.049; OR: 8.42, < 0.001), chemotherapy (OR: 0.43, = 0.02; OR: 0.25, = 0.007), and NRS average scores (OR: 0.38, = 0.02; OR: 0.14, < 0.001) were independent factors associated with ADL and QOL. : Patients with bone metastases who underwent conservative treatment through BMCBs exhibited an increase in QOL without a decline in ADL. The presence of spinal cord paralysis, absence of chemotherapy, and poor pain control were associated with a higher risk of deterioration in ADL and QOL.
Topics: Humans; Quality of Life; Bone Neoplasms; Activities of Daily Living; Female; Male; Retrospective Studies; Middle Aged; Aged; Conservative Treatment; Aged, 80 and over; Adult
PubMed: 38929523
DOI: 10.3390/medicina60060906 -
Medicina (Kaunas, Lithuania) May 2024A ganglion cyst is a benign mass consisting of high-viscosity mucinous fluid. It can originate from the sheath of a tendon, peripheral nerve, or joint capsule....
A ganglion cyst is a benign mass consisting of high-viscosity mucinous fluid. It can originate from the sheath of a tendon, peripheral nerve, or joint capsule. Compressive neuropathy caused by a ganglion cyst is rarely reported, with the majority of documented cases involving peroneal nerve palsy. To date, cases demonstrating both peroneal and tibial nerve palsies resulting from a ganglion cyst forming on a branch of the sciatic nerve have not been reported. In this paper, we present the case of a 74-year-old man visiting an outpatient clinic complaining of left-sided foot drop and sensory loss in the lower extremity, a lack of strength in his left leg, and a decrease in sensation in the leg for the past month without any history of trauma. Ankle dorsiflexion and great toe extension strength on the left side were Grade I. Ankle plantar flexion and great toe flexion were Grade II. We suspected peroneal and tibial nerve palsy and performed a screening ultrasound, which is inexpensive and rapid. In the operative field, several cysts were discovered, originating at the site where the sciatic nerve splits into peroneal and tibial nerves. After successful surgical decompression and a series of rehabilitation procedures, the patient's neurological symptoms improved. There was no recurrence.
Topics: Humans; Aged; Male; Ganglion Cysts; Peroneal Neuropathies; Peroneal Nerve; Tibial Nerve; Paralysis
PubMed: 38929493
DOI: 10.3390/medicina60060876