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1.
Orthop J Sports Med ; 12(5): 23259671241243345, 2024 May.
Article in English | MEDLINE | ID: mdl-38708007

ABSTRACT

Background: Hamstring strains are common among elite athletes, but their effect on return to the same level of play in American football has been incompletely characterized. Purpose: Data on National Collegiate Athletics Association Division I college football players with acute hamstring strains were gathered to identify the effects these injuries have on both return to play and athletic performance regarding velocity, workload, and acceleration. Study Design: Case Series; Level of evidence, 4. Methods: Injury data for a single Division I football team were prospectively recorded over a 4-year period. Players wore global navigation satellite system and local positioning system (GNSS/LPS) devices to record movement data in practices and games. The practice and game data were cross-referenced to evaluate players with isolated acute hamstring strains. Comparisons were made regarding players' pre- and postinjury ability to maintain high velocity (>12 mph [19.3 kph]), maximal velocity, triaxial acceleration, and inertial movement analysis (IMA). There were 58 hamstring injuries in 44 players, of which 25 injuries from 20 players had GNSS/LPS data. Results: Players were able to return to play from all 25 injury incidences at a mean of 9.2 days. At the final mean follow-up of 425 days, only 4 players had reached preinjury function in all measurements; 12 players were able to return in 2 of the 4 metrics; and only 8 players reached their preinjury ability to maintain high velocity. For those who did not achieve this metric, there was a significant difference between pre- and postinjury values (722 vs 442 m; P = .016). A total of 14 players were able to regain their IMA. Players who returned to prior velocity or acceleration metrics did so at a mean of 163 days across all metrics. Conclusion: While players may be able to return to play after hamstring strain, many players do not reach preinjury levels of acceleration or velocity, even after 13.5 months. Further studies are needed to confirm these findings, assess clinical relevance on imaging performance, and improve hamstring injury prevention and rehabilitation.

2.
Antioxidants (Basel) ; 13(5)2024 May 16.
Article in English | MEDLINE | ID: mdl-38790713

ABSTRACT

Cyanobacteria in recent times have been touted to be a suitable source for the discovery of novel compounds, including antioxidants and antibiotics, due to their large arsenal of metabolites. This study presents the in vitro antioxidant and in silico evaluation of Cylindrospermum alatosporum NR125682 and Loriellopsis cavenicola NR117881, isolated from freshwater ponds around the campus of the University of Zululand, South Africa. The isolates were confirmed using 16S rRNA. Various crude extracts of the isolated microbes were prepared through sequential extraction using hexane, dichloromethane, and 70% ethanol. The chemical constituents of the crude extracts were elucidated by FTIR and GC-MS spectroscopy. The antioxidant potential of the extracts was determined by the free radical (DPPH, ABTS, •OH, and Fe2+) systems. Molecular docking of the major constituents of the extracts against ß-lactamase was also evaluated. GC-MS analysis indicated the dominating presence of n-alkanes. The extracts exhibited varying degrees of antioxidant activity (scavenging of free radicals; an IC50 range of 8-10 µg/mL was obtained for ABTS). A good binding affinity (-6.6, -6.3 Kcal/mol) of some the organic chemicals (diglycerol tetranitrate, and 2,2-dimethyl-5-(3-methyl-2-oxiranyl)cyclohexanone) was obtained following molecular docking. The evaluated antioxidant activities, coupled with the obtained docking score, potentiates the antimicrobial activity of the extracts.

3.
ACS Pharmacol Transl Sci ; 7(4): 1142-1168, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38633582

ABSTRACT

The neuropeptide Y (NPY) Y4 receptor (Y4R), a member of the family of NPY receptors, is physiologically activated by the linear 36-amino acid peptide pancreatic polypeptide (PP). The Y4R is involved in the regulation of various biological processes, most importantly pancreatic secretion, gastrointestinal motility, and regulation of food intake. So far, Y4R binding affinities have been mostly studied in radiochemical binding assays. Except for a few fluorescently labeled PP derivatives, fluorescence-tagged Y4R ligands with high affinity have not been reported. Here, we introduce differently fluorescence-labeled (Sulfo-Cy5, Cy3B, Py-1, Py-5) Y4R ligands derived from recently reported cyclic hexapeptides showing picomolar Y4R binding affinity. With pKi values of 9.22-9.71 (radioligand competition binding assay), all fluorescent ligands (16-19) showed excellent Y4R affinity. Y4R saturation binding, binding kinetics, and competition binding with reference ligands were studied using different fluorescence-based methods: flow cytometry (Sulfo-Cy5, Cy3B, and Py-1 label), fluorescence anisotropy (Cy3B label), and NanoBRET (Cy3B label) binding assays. These experiments confirmed the high binding affinity to Y4R (equilibrium pKd: 9.02-9.9) and proved the applicability of the probes for fluorescence-based Y4R competition binding studies and imaging techniques such as single-receptor molecule tracking.

4.
J Med Entomol ; 61(1): 245-249, 2024 01 12.
Article in English | MEDLINE | ID: mdl-37897421

ABSTRACT

White-tailed deer Odocoileus virginianus (Zimmermann) (Artiodactyla: Cervidae) are the main host for adult Ixodes scapularis Say (Acari: Ixodidae) (blacklegged tick) and all stages of Amblyomma americanum Linnaeus (Acari: Ixodidae) (lone star tick). However, literature describing the feeding and reproductive parameters of these tick species when feeding on this host is limited. We experimentally infested white-tailed deer with adult pairs of either I. scapularis or A. americanum to improve our understanding of these tick-host relationships. Our study used tick-naïve white-tailed deer and restricted host grooming throughout the infestation. For I. scapularis, the days to repletion (mean ±â€…SE, 6.04 ±â€…0.07), engorgement weight of replete females (0.20 ±â€…0.0032 g), duration of oviposition (32 ±â€…0.45 d), egg mass weight (0.10 ±â€…0.0027 g), and number of eggs laid per tick (1,803.00 ±â€…49.00) were recorded. Data from A. americanum were also recorded, including days to repletion (11.00 ±â€…0.063), engorgement weight of replete females (0.63 ±â€…0.025 g), duration of oviposition (37.00 ±â€…1.30 d), egg mass weight (0.34 ±â€…0.017 g), and number of eggs laid per tick (5,873.00 ±â€…291.00). These biological parameter data could be used as variables in models (e.g., LYMESIM 2.0) to determine how white-tailed deer influence I. scapularis and A. americanum populations in nature, and to evaluate the protective efficacy of tick-antigen-based antitick vaccines.


Subject(s)
Deer , Ixodes , Ixodidae , Tick Infestations , Animals , Female , Amblyomma , Tick Infestations/veterinary
5.
J Med Chem ; 66(19): 13788-13808, 2023 10 12.
Article in English | MEDLINE | ID: mdl-37773891

ABSTRACT

The family of human neuropeptide Y receptors (YRs) comprises four subtypes (Y1R, Y2R, Y4R, and Y5R) that are involved in the regulation of numerous physiological processes. Until now, Y4R binding studies have been predominantly performed in hypotonic sodium-free buffers using 125I-labeled derivatives of the endogenous YR agonists pancreatic polypeptide or peptide YY. A few tritium-labeled Y4R ligands have been reported; however, when used in buffers containing sodium at a physiological concentration, their Y4R affinities are insufficient. Based on the cyclic hexapeptide UR-AK86C, we developed a new tritium-labeled Y4R radioligand ([3H]UR-JG102, [3H]20). In sodium-free buffer, [3H]20 exhibits a very low Y4R dissociation constant (Kd 0.012 nM). In sodium-containing buffer (137 mM Na+), the Y4R affinity is lower (Kd 0.11 nM) but still considerably higher compared to previously reported tritiated Y4R ligands. Therefore, [3H]20 represents a useful tool compound for the determination of Y4R binding affinities under physiological-like conditions.


Subject(s)
Neuropeptide Y , Peptides, Cyclic , Humans , Neuropeptide Y/chemistry , Peptides, Cyclic/pharmacology , Tritium , Receptors, Neuropeptide Y/metabolism , Ligands , Sodium
6.
J Med Chem ; 66(14): 9642-9657, 2023 07 27.
Article in English | MEDLINE | ID: mdl-37440703

ABSTRACT

The G-protein-coupled Y4-receptor (Y4R) and its endogenous ligand, pancreatic polypeptide (PP), suppress appetite in response to food intake and, thus, are attractive drug targets for body-weight control. The C-terminus of human PP (hPP), T32-R33-P34-R35-Y36-NH2, penetrates deep into the binding pocket with its tyrosine-amide and di-arginine motif. Here, we present two C-terminally amidated α,γ-hexapeptides (1a/b) with sequence Ac-R31-γ-CBAA32-R33-L34-R35-Y36-NH2, where γ-CBAA is the (1R,2S,3R)-configured 2-(aminomethyl)-3-phenylcyclobutanecarboxyl moiety (1a) or its mirror image (1b). Both peptides bind the Y4R (Ki of 1a/b: 0.66/12 nM) and act as partial agonists (intrinsic activity of 1a/b: 50/39%). Their induced-fit binding poses in the Y4R pocket are unique and build ligand-receptor contacts distinct from those of the C-terminus of the endogenous ligand hPP. We conclude that energetically favorable interactions, although they do not match those of the native ligand hPP, still guarantee high binding affinity (with 1a rivaling hPP) but not the maximum receptor activation.


Subject(s)
Cyclobutanes , Neuropeptide Y , Humans , Neuropeptide Y/metabolism , Ligands , Receptors, Neuropeptide Y/metabolism , Pancreatic Polypeptide/metabolism
7.
Orthop J Sports Med ; 11(1): 23259671221141664, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36743735

ABSTRACT

Background: The prevalence of meniscal tears in patients with anterior cruciate ligament (ACL) injury increases with extended time between injury and ACL reconstruction. Purpose/Hypothesis: The purpose of this study was to determine if there is a relationship between time from magnetic resonance imaging (MRI) to ACL reconstruction and the predictive value of MRI to diagnose meniscal tears in the young active population. It was hypothesized that increased time between MRI and ACL reconstruction would lead to a decrease in the negative predictive value of MRI in diagnosing meniscal tears, as more injuries may accrue over time in the ACL-deficient knee. Study Design: Case series; Level of evidence, 4. Methods: Included were patients aged 13 to 25 years at the authors' institution who underwent primary ACL reconstruction from January 2017 to June 2020. Time from MRI to surgery as well as descriptions of medial and lateral meniscal tears on both MRI and operative reports were documented. Time from MRI to surgery was divided into 4 intervals: 0 to 6 weeks, >6 weeks to 3 months, >3 to 6 months, and beyond 6 months. Multivariable analysis was used to determine the positive and negative predictive values of MRI in diagnosing a meniscal tear as compared with arthroscopic findings. Results: A total of 432 patients were included with a mean age of 17.9 ± 3.4 years. The mean time from MRI to surgery was 70.5 ± 98 days. There was a significant decrease in the negative predictive value of MRI to identify a medial meniscal tear in patients who underwent ACL reconstruction >6 months after imaging (odds ratio, 0.16 [95% CI, 0.05-0.53]; P = .003). This same relationship was not shown for lateral meniscal tears, nor was any other predictor significant. Conclusion: The utility of MRI to rule out a medial meniscal tear significantly diminished in the young athletic population when >6 months passed between MRI and ACL reconstruction. These data suggest these tears occur between the time of the MRI and surgery and that the medial meniscus is more susceptible than the lateral meniscus to new injury once the ACL has torn.

8.
Am J Sports Med ; 51(2): 398-403, 2023 02.
Article in English | MEDLINE | ID: mdl-36533946

ABSTRACT

BACKGROUND: Delayed anterior cruciate ligament (ACL) reconstruction (ACLR) is associated with an increased risk of meniscal injury. Limited data are available regarding the relationship between surgical delay and meniscal repairability in the setting of ACLR in young patients. PURPOSE: To determine whether time from ACL injury to primary ACLR was associated with the incidence of medial and/or lateral meniscal repair in young athletes who underwent meniscal treatment at the time of ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Records were retrospectively reviewed for patients aged 13 to 25 years who underwent primary ACLR between January 2017 and June 2020 by surgeons from a single academic orthopaedic surgery department. Demographic data were collected, and operative reports were reviewed to document all concomitant pathologies and procedures. Univariable and multivariable logistic regression analyses were used to determine factors associated with meniscal repair, including time elapsed from ACL injury to surgery. RESULTS: Concomitant meniscal tears were identified and treated in 243 of 427 patients; their mean age was 17.9 ± 3.3 years, and approximately half (47.7%) of patients were female. There were 144 (59.3%) medial tears treated and 164 (67.5%) lateral tears treated; 65 (26.7%) patients had both medial and lateral tears treated. Median time from ACL injury to ACLR was 2.4 months (interquartile range, 1.4-4.7 months). Adjusted univariate analysis showed a statistically significant correlation between medial meniscal repair and time to surgery, with a 7% decreased incidence of medial meniscal repair per month elapsed between injury and surgery (odds ratio, 0.93 per month; 95% CI, 0.89-0.98; P = .006). No similar relationship was found between lateral meniscal repair and time to surgery (odds ratio, 1.02; 95% CI, 0.99-1.06; P = .24). CONCLUSION: In the setting of concomitant ACL and meniscal injuries, surgical delay decreased the incidence of medial meniscal repair in young athletes by 7% per month from time of injury.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Tibial Meniscus Injuries , Humans , Female , Adolescent , Young Adult , Adult , Male , Anterior Cruciate Ligament Injuries/surgery , Menisci, Tibial/surgery , Retrospective Studies , Case-Control Studies , Tibial Meniscus Injuries/surgery , Anterior Cruciate Ligament Reconstruction/methods , Athletes
9.
J Shoulder Elbow Surg ; 31(12): 2671-2677, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35931330

ABSTRACT

Repetitive stress injuries to the rotator cuff, and particularly the supraspinatus tendon (SST), are highly prevalent and debilitating. These injuries typically occur through the application of cyclic load below the threshold necessary to cause acute tears, leading to accumulation of incremental damage that exceeds the body's ability to heal, resulting in decreased mechanical strength and increased risk of frank rupture at lower loads. Consistent progression of fatigue damage across multiple model systems suggests a generalized tendon response to overuse. This finding may allow for interventions before gross injury of the SST occurs. Further research into the human SST response to fatigue loading is necessary to characterize the fatigue life of the tendon, which will help determine the frequency, duration, and magnitude of load spectra the SST may experience before injury. Future studies may allow in vivo SST strain analysis during specific activities, generation of a human SST stress-cycle curve, and characterization of damage and repair related to repetitive tasks.


Subject(s)
Rotator Cuff Injuries , Tendon Injuries , Humans , Rotator Cuff/physiology , Rotator Cuff Injuries/complications , Rotator Cuff Injuries/surgery , Tendon Injuries/complications , Tendon Injuries/surgery , Tendons , Fatigue , Biomechanical Phenomena
10.
J Shoulder Elbow Surg ; 31(12): 2678-2682, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35803551

ABSTRACT

Overuse injuries of the rotator cuff, particularly of the supraspinatus tendon (SST), are highly prevalent and debilitating in work, sport, and daily activities. Despite the clinical significance of these injuries, there remains a large degree of uncertainty regarding the pathophysiology of injury, optimal methods of nonoperative and operative repair, and how to adequately assess tendon injury and healing. The tendon response to fatigue damage resulting from overuse is different from that of acute rupture and results in either an adaptive (healing) or a maladaptive (degenerative) response. Factors associated with the degenerative response include increasing age, smoking, hypercholesterolemia, biological sex (variable by tendon), diabetes mellitus, and excessive load post fatigue damage. After injury, the average healing rate of tendon is approximately 1% per day and may be significantly influenced by biologic sex (females have lower collagen synthesis rates) and excessive load after damage. Although magnetic resonance imaging (MRI) is considered the gold standard in assessing acute tears as well as tendinopathic change in the SST, ultrasonography has proven to be a valuable tool to measure tendinopathic change in real time. Ultrasonography can determine multiple mechanical and structural parameters of the SST that are altered in fatigue loading. Thus, ultrasonography may be utilized to understand how these parameters change in response to SST overuse, and may aid in determining the activity level that places the SST at greater risk of rupture.


Subject(s)
Rotator Cuff Injuries , Tendon Injuries , Humans , Female , Rotator Cuff/pathology , Rotator Cuff Injuries/diagnostic imaging , Rotator Cuff Injuries/surgery , Rotator Cuff Injuries/pathology , Tendons/surgery , Tendon Injuries/diagnostic imaging , Tendon Injuries/surgery , Rupture/surgery , Fatigue/pathology
11.
Arthrosc Sports Med Rehabil ; 4(3): e1097-e1102, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35747627

ABSTRACT

Purpose: To compare stiffness, strain, and load to failure of 4- versus 5-strand hamstring anterior cruciate ligament reconstruction human tendon allografts with femoral suspensory and tibial interference screw fixation. Methods: Allograft hamstring tendons were used to create 10 four-strand (4S) and 10 five-strand (5S) grafts. Grafts were fixed to a uniaxial electromechanical load system via a femoral cortical suspensory button and a bioabsorbable interference screw in bone analogue. Grafts were cycled from 100 Newtons (N) to 250 N for 1,000 repetitions at 0.5 hertz before load to failure testing. Cyclic displacement was defined as the difference in graft length from the first 20 to 30 cycles compared with the last 10 cycles. Trials were recorded on a high-definition camera to allow for digital image correlation analysis. Results: Cyclic displacement more than 1,000 cycles was significantly lower in the 4S compared with the 5S group (0.87 vs 1.11 mm, P = .037). Digital image correlation analysis confirmed that the fifth strand elongated more than the other 4 strands in the 5S constructs (6.1% vs 3.9%, P = .032). Load to failure was greater in the 4S compared with the 5S group but not statistically significant (762 vs 707 N, P = .35). Stiffness was similar between constructs (138.5 vs 138.3 N/mm, P = .96). Conclusions: Compared with cyclically loaded 4S hamstring grafts, the 5S grafts had significantly increased displacement over time in a model of femoral suspensory and tibial interference screw fixation. Clinical Relevance: Anterior cruciate ligament reconstruction with hamstring tendon autograft is a commonly performed surgery with excellent outcomes. It has been shown that graft diameter influences these outcomes. As surgeons use larger grafts, it is important to investigate how these constructs may affect the outcomes of surgery.

12.
Plants (Basel) ; 11(7)2022 Mar 28.
Article in English | MEDLINE | ID: mdl-35406876

ABSTRACT

Tigernut or 'chufa' (Cyperus esculentus L. var. sativus) is gaining popularity in the United States as a high energy tuber crop known for sweet and chewy taste, 40-45% gluten-free digestible carbohydrate, high dietary fiber content, healthful fatty acid profile (73% monounsaturated, 18% saturated, 9% polyunsaturated-similar to olive oil), high oleic acid, and high P, K, and vitamins C. E. Tigernut tubers were obtained from specialty crop markets in central NJ and purchased online from commercial distributors as propagules for transplants for hoop house and field production studies. Nine tigernut selections were also evaluated under NJ hoop house culture conditions for growth habit and in the field for adaptation and productivity We concluded that tigernut production is feasible in NJ based on the results of these experiments. The growth patterns of three selections (GH, MV and SK) were studied and characterized. Foliage growth was similar in the three selections. Plant height ranged from an average of 90 cm in GH to 110 cm in MV and SK; side shoot production capacity ranged from 13 shoots per propagule in GH to 20 or more in MV and SK over 14 weeks. Over 99% of tubers in MV and SK were located within the upper 5 cm of the growth media (Pro-Mix BX brand) but tubers of GH were observed at greater soil depths (~20 cm). Tubers varied from spherical (round) in shape in GH and SK to oblong (elongated) in MV. In the field the best growth and tuber yields from NG3 and T-USA selections were obtained under black or white-over-black plastic mulch in conventionally managed plots. Tubers showed high levels of Fe (168-218 ppm) and Zn (39-50 ppm) implying that they should be a good source of these essential elements in human diet. Studies also showed that the tigernut tuber cannot survive the cold winter months in the field in NJ, therefore minimizing the fear of "tigernut invasion" of agronomic fields in NJ and similar agroecosystems.

13.
Skeletal Radiol ; 51(8): 1611-1621, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35122144

ABSTRACT

OBJECTIVE: To compare the diagnostic performance of direct magnetic resonance arthrography (MRA) for labral lesions during conventional, abduction and external rotation (ABER), conventional plus abduction, and external rotation (ABER) positioning by using a systematic review and meta-analysis. MATERIALS AND METHODS: A comprehensive literature search was performed on the two main concepts of magnetic resonance arthrography: extremity position and labral lesions. Inclusion criteria consisted of original studies that assessed the diagnostic accuracy of MR arthrography in ABER and conventional position alone or combined for the diagnosis of labral lesions by using surgical findings as the reference standard. Meta-analyses were performed that compared MR arthrography during conventional positioning, ABER, and conventional plus ABER positioning. RESULTS: Nine studies met the inclusion and exclusion criteria. A total of 733, 504, and 313 lesions assessed by conventional MRA, ABER MRA, and conventional plus ABER MRA, respectively, were included in our analysis. Pooled sensitivities of MRA in conventional, ABER, and conventional plus ABER position for labral tear diagnosis were 81.5%, 81.6%, and 95.7%, respectively. Pooled specificities of MRA in conventional, ABER, and conventional plus ABER position for labral tear diagnosis were 88.8%, 85.6%, and 94.5%, respectively. Summary receiver operator characteristic (ROC) curve demonstrated improved accuracy of conventional plus ABER MRA compared with conventional MRA or ABER MRA with the area under the curve (AUC) of 0.99, 0.90, and 0.88, respectively. CONCLUSION: Conventional plus ABER MRA showed increased diagnostic accuracy compared to both ABER MRA and conventional MRA alone in the diagnosis of labral lesions.


Subject(s)
Arthrography , Shoulder Joint , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Sensitivity and Specificity , Shoulder Joint/diagnostic imaging
14.
Ocul Immunol Inflamm ; 30(4): 907-914, 2022 May 19.
Article in English | MEDLINE | ID: mdl-33596386

ABSTRACT

PURPOSE/OBJECTIVES: to evaluate new onset uveitis or reactivated uveitis by biologic agents and characterize their features. MATERIALS AND METHODS: This is a multicenter, retrospective case series. Patients under biologic therapy were included if they developed uveitis for the first time or experienced intraocular inflammation which was different in location or laterality to previous inflammation. RESULTS: Sixteen patients were identified. The underlying disorders included ankylosing spondylitis, juvenile idiopathic arthritis, rheumatoid arthritis, and Behçet's Disease. The biologic agents associated with a first episode of uveitis (n = 11) or with a new recurrence of uveitis (n = 5) were etanercept, adalimumab, abatacept, infliximab, and golimumab. Sarcoidosis based on bihilar lymphadenopathy, other computer tomography-findings, or biopsy was diagnosed in five patients under therapy with etanercep, adalimumab, and abatacept. Additionally, seven patients developed clinical changes in their uveitis pattern, suggesting sarcoid uveitis. CONCLUSIONS: Biologic treatment-induced uveitis often presents as granulomatous disease.


Subject(s)
Antirheumatic Agents , Biological Products , Sarcoidosis , Uveitis , Abatacept/adverse effects , Adalimumab/adverse effects , Antirheumatic Agents/adverse effects , Biological Factors/therapeutic use , Biological Products/adverse effects , Humans , Inflammation/drug therapy , Infliximab/adverse effects , Retrospective Studies , Sarcoidosis/chemically induced , Sarcoidosis/complications , Sarcoidosis/diagnosis , Uveitis/chemically induced , Uveitis/diagnosis , Uveitis/drug therapy
15.
J Med Chem ; 64(22): 16746-16769, 2021 11 25.
Article in English | MEDLINE | ID: mdl-34748345

ABSTRACT

The family of neuropeptide Y (NPY) receptors comprises four subtypes (Y1R, Y2R, Y4R, Y5R), which are addressed by at least three endogenous peptides, i.e., NPY, peptide YY, and pancreatic polypeptide (PP), the latter showing a preference for Y4R. A series of cyclic oligopeptidic Y4R ligands were prepared by applying a novel approach, i.e., N-terminus to arginine side-chain cyclization. Most peptides acted as Y4R partial agonists, showing up to 60-fold higher Y4R affinity compared to the linear precursor peptides. Two cyclic hexapeptides (18, 24) showed higher Y4R potency (Ca2+ aequorin assay) and, with pKi values >10, also higher Y4R affinity compared to human pancreatic polypeptide (hPP). Compounds such as 18 and 24, exhibiting considerably lower molecular weight and considerably more pronounced Y4R selectivity than PP and previously described dimeric peptidic ligands with high Y4R affinity, represent promising leads for the preparation of labeled tool compounds and might support the development of drug-like Y4R ligands.


Subject(s)
Arginine/chemistry , Neuropeptide Y/metabolism , Receptors, Neuropeptide Y/metabolism , Amino Acid Sequence , Cyclization , HEK293 Cells , Humans , Ligands , Molecular Docking Simulation , Protein Binding , Receptors, Neuropeptide Y/chemistry
17.
Case Rep Ophthalmol ; 12(1): 311-314, 2021.
Article in English | MEDLINE | ID: mdl-34054476

ABSTRACT

A 73-year-old man presented 3 days after intravitreal injection (IVI) with bevacizumab for treatment of neovascular age-related macular degeneration with pain and redness around the injection site. Examination showed conjunctival edema and injection around the injection site and a central infiltrate at the injection site consistent with infection of Tenon's capsule and the conjunctiva. Infection of a vitreous wick was considered, but vitreous inflammation was not present. Acute bacterial tenonitis and conjunctivitis were diagnosed, and the patient was prescribed topical antibiotic drops. The patient's symptoms were resolved within 48 h following the use of topical antibiotic drops, so a culture was not performed. The patient did not develop endophthalmitis. To our knowledge, this is the first reported case of acute bacterial tenonitis and conjunctivitis of the injection site following IVI. Even with the use of betadine, infection of Tenon's capsule and the conjunctiva may occur after IVI and must be differentiated from other causes of postinjection ocular redness such as chemical irritation of the ocular surface, corneal abrasions, and endophthalmitis.

18.
Niger J Clin Pract ; 24(4): 546-550, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33851676

ABSTRACT

BACKGROUND: Orbital cellulitis, also called postseptal cellulitis, is an infection of contents of the orbit (periorbital fat, neurovascular bundle, and the extraocular muscles). It should be differentiated from preseptal (periorbital) cellulitis which is a lesion of the anterior portion of the eyelid. However, both preseptal and postseptal cellulitis could present in a similar way with eye pain, edema, and erythema. AIM: The aim of the study was to review patients with orbital cellulitis as a complication of odontogenic cervicofacial infections seen in a Nigerian tertiary care facility. PATIENTS AND METHODS: A retrospective analysis of cases of odontogenic cervicofacial infections complicated by orbital infections that presented at a Nigerian tertiary health facility between January 2006 and September 2019 was conducted. RESULTS: A total of 10 patients with cervicofacial infections who presented with 11 orbital infections as a complication were retrieved for this study. They were six males and four females; male to female ratio was 1.5:1. Median age was 33.5 years (mean age was 34.3 years, range was 22-47 years). Based on clinical features and results of available imaging, orbital infections using the classification by Chandler et al., (1970), were one cases of type I (9.1%), seven cases (63.6%) of type II and two cases (18.2%) of type IV and one case (9.1%) of type V. There was no case of type III. CONCLUSION: Cervicofacial infections could arise from upper posterior teeth. These infections could spread into the orbit causing cellulitis especially type II.


Subject(s)
Orbital Cellulitis , Tomography, X-Ray Computed , Adult , Anti-Bacterial Agents/therapeutic use , Cellulitis/drug therapy , Cellulitis/etiology , Edema/drug therapy , Female , Humans , Male , Middle Aged , Orbit , Orbital Cellulitis/drug therapy , Orbital Cellulitis/etiology , Retrospective Studies , Young Adult
19.
Invest Ophthalmol Vis Sci ; 62(1): 17, 2021 01 04.
Article in English | MEDLINE | ID: mdl-33444430

ABSTRACT

Purpose: To characterize inheritance, penetrance, and trinucleotide repeat expansion stability in Fuchs endothelial corneal dystrophy (FECD). Methods: One thousand unrelated and related subjects with and without FECD were prospectively recruited. CTG18.1 repeat length (CTG18.1L) was determined via short tandem repeat assay and Southern blotting of leukocyte DNA. Multivariable logistic regression and generalized estimating equation models were employed. Results: There were 546 unrelated FECD cases (67.6% female; 70 ± 10 years) and 235 controls (63.8% female; 73 ± 8 years; all ≥ 50 years). CTG18.1 expansion (CTG18.1exp+) was observed in 424 (77.7%) cases and 18 (7.7%) controls (P = 2.48 × 10-44). CTG18.1 expansion was associated with FECD severity (P = 5.62 × 10-7). The family arm of the study included 331 members from 112 FECD-affected families; 87 families were CTG18.1exp+. Autosomal dominant inheritance with variable expression of FECD was observed, regardless of expansion status. FECD penetrance of CTG18.1 expansion increased with age, ranging from 44.4% in the youngest (19-46 years) to 86.2% in the oldest (64-91 years) age quartiles. Among 62 parent-offspring transmissions of CTG18.1exp+, 48 (77.4%) had a change in CTG18.1L ≤ 10 repeats, and eight (12.9%) were ≥50 repeats, including five large expansions (∼1000-2000 repeats) that contracted. Among 44 offspring who did not inherit the CTG18.1exp+ allele, eight (18.2%) exhibited FECD. Conclusions: CTG18.1 expansion was highly associated with FECD but demonstrated incomplete penetrance. CTG18.1L instability occurred in a minority of parent-offspring transmissions, with large expansions exhibiting contraction. The observation of FECD without CTG18.1 expansion among family members in CTG18.1exp+ families highlights the complexity of the relationship between the FECD phenotype and CTG18.1 expansion.


Subject(s)
Fuchs' Endothelial Dystrophy/genetics , Transcription Factor 4/genetics , Trinucleotide Repeat Expansion/genetics , Adult , Aged , Aged, 80 and over , Blotting, Southern , DNA/genetics , Female , Genetic Predisposition to Disease , Genotype , Humans , Inheritance Patterns , Male , Microsatellite Repeats , Middle Aged , Pedigree , Penetrance , Polymerase Chain Reaction , Polymorphism, Genetic , Prospective Studies , Young Adult
20.
Med Sci Sports Exerc ; 53(1): 115-123, 2021 01.
Article in English | MEDLINE | ID: mdl-32694365

ABSTRACT

INTRODUCTION: After anterior cruciate ligament reconstruction surgery, returning the knee to previous levels of strength and function is challenging, with the failure to do so associated with an increased risk of reinjury and long-term degenerative problems. Blood flow restriction (BFR) is gaining popularity as a rehabilitation technique; however, its effects on the mechanics of these exercises have not been fully explored. In this study, we aimed to determine the acute effects of BFR on the performance of a step-up exercise protocol and to assess the acceptability of the technique. METHODS: Twenty individuals (12 female/8 male; mean age, 30.6 yr) who had recently undergone anterior cruciate ligament reconstruction and 20 controls (11 female/9 male, mean age 28.0 yr) performed a step-up exercise protocol with and without BFR. Lower limb kinematics and kinetics were measured and compared between groups and conditions. Testing was completed in June 2019. RESULTS: Participants in both groups had increased external rotation of the tibia of 2° (P < 0.001) and reductions in knee flexion and rotation torques around the joint of around 50% (P < 0.001) when using BFR compared with nonrestricted step-up exercise. The intervention was found to increase the difficulty of the exercise and induce moderate levels of discomfort (P < 0.001). CONCLUSION: The present study provides cautious support for the use of BFR, showing that there are minimal changes in knee joint mechanics when performing the same exercise without BFR, and that the changes do not increase joint torques at the knee. From an acute biomechanical perspective, the intervention appears safe to use under qualified supervision; however, effects of repetitive use and long-term outcomes should be monitored.


Subject(s)
Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction/rehabilitation , Exercise Therapy/methods , Regional Blood Flow , Thigh/blood supply , Adult , Biomechanical Phenomena , Cross-Sectional Studies , Female , Hip/physiology , Humans , Kinetics , Knee/physiology , Male , Rotation , Tibia/physiology , Time and Motion Studies
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