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Objective: Correction of a proximal tibial valgus deformity., Indications: Lateral osteoarthritis of the knee or cartilage damage in a valgus deformity > 5° with a medial proximal tibial angle (MPTA) > 90°., Contraindications: Medial proximal tibial angle < 90°, medial cartilage damage, medial meniscus loss., Surgical Technique: Skin incision medial of the tibial tuberosity approximately 8-10 cm. Insertion of two converging guidewires directly above the pes anserinus, ascending obliquely, and ending at the tip of the fibula. Control of the wire position with the image intensifier. Osteotomy with an oscillating saw. Removal of the wedge and closure of the osteotomy. Osteosynthesis with a medial angle-stable plate., Postoperative Management: Partial load bearing with 10-20 kg for 2 weeks, then step-wise increase in load. Mobility: free., Results: We performed this surgery in the manner described in 21 patients with lateral osteoarthritis or cartilage damage (17 men, 4 women, average age: 51 years). The valgus deformity was reduced from an average of 5.6 to -0.5°. The KOOS-PS (Knee Injury and Osteoarthritis Outcome Score-Physical Function Short-form) score decreased significantly from 39.1 ± 14 to 25.8 ± 20 points., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: Correction of a severe tibial varus deformity near the knee joint with only a slight influence on leg length and patella height., Indications: Medial osteoarthritis and/or cartilage damage with a severe varus deformity > 10° with a medial proximal tibial angle (MPTA) < 80°., Contraindications: Femoral varus deformity with lateral distal femoral angle > 91°, severe lateral cartilage damage, lateral osteoarthritis, lateral meniscus loss., Surgical Technique: Skin incision of approx. 8-10 cm between the tibial tuberosity and the head of the fibula. Exploration of the peroneal nerve. Detachment of the extensors. Insertion of an obliquely ascending guidewire ending approximately 10 mm below the medial articular surface. Insertion of a second guidewire. This aims at the middle of the first wire (hemi wedge). Check the wire position under fluoroscopy. Osteotomy with an oscillating saw under cooling. Removal of the wedge and closure of the osteotomy. Percutaneous needling of the medial collateral ligament with a cannula to carefully lengthen the ligament. Check the correction result with a metal rod. Osteosynthesis with lateral angle-stable plate., Postoperative Management: Partial weight-bearing with 10 kg for 6 weeks postoperatively, free range of motion., Results: Reports from the literature show that good clinical results can be achieved with this procedure for severe tibial varus deformities. Postoperative leg length discrepancies are less common with this procedure than with laterally closing osteotomy., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: Reconstruction of a patellar tendon defect in the event of a chronic rupture., Indications: Chronic rupture of the patellar tendon due to delayed diagnosis or failure of primary refixation with a dehiscence that does not allow for anatomical refixation without patellar tendon shortening., Contraindications: Infection., Surgical Technique: Approximately 15 cm long incision from the tibial tuberosity to the patella. Depicting the rupture. Debridement of the tendon and insertion. Suture in the quadriceps tendon and distalization of the patella. If sufficient distalization of the patella is not possible, optionally perform a VY-plasty of the quadriceps tendon. Measuring the dehiscence. Securing the height of the patella by applying a patellotibial cerclage (strong suture cord). Extension of an existing tendon stump using a Z-plasty. Creation of 2 bone tunnels (diameter approx. 5 mm) in the patella and the tibial tuberosity. Insertion of an autologous or allogeneic semitendinosus tendon transplant and securing it by knotting the retaining threads in front of the tibial tuberosity., Postoperative Management: Six weeks of partial weight-bearing with 10 kg of body weight in a straight, removable splint. Range of movement: weeks 1-4 E/F 0-0-60°, weeks 5-6 E/F 0-0-90°., Results: Seven patients who underwent this surgery as described above had a minimum follow-up of 2 years. Secondary lengthening of the quadriceps tendon had to be performed twice due to excessive retraction. All patients were able to perform active extension postoperatively. The Lysholm score rose from 49.3 to 83.2 points. No further rupture was detectable in the final ultrasound examination., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Benign prostatic hyperplasia (BPH) is a chronic disorder that inflicts severe symptoms on middle-aged men. The current study compared the effects of tadalafil and tamsulosin on urological parameters after 3 and 6 months of therapy. A retrospective case-control study was conducted, in which 100 patients with moderately severe BPH were divided into two groups based on their treatment: 50 patients were given tamsulosin 0.4 mg/day and group 50 patients were administered tadalafil 5 mg daily. All patients continued therapy for approximately 6 months, and their urological parameters were assessed at baseline and after 3 and 6 months. There was no significant difference in the overall effect on the International Prostate Symptom Score at the end of the study using two-way ANOVA analysis ( P = 0.448). The intercourse number was significantly improved by tadalafil compared to tamsulosin ( P < 0.001). The prostatic-specific antigen, postvoiding residual, and prostatic volumes were not significantly different between tadalafil and tamsulosin ( P = 0.198, 0.163, and 0.183, respectively). In conclusion, tadalafil, 5 mg once daily, appears to have similar efficacy to tamsulosin, with significant improvement in the patient's erectile function. Tadalafil can be used for 6 months for moderate-to-severe lower urinary tract symptoms., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Advanced Pharmaceutical Technology & Research.)

Circadian clocks evolved to enable organisms to anticipate and prepare for periodic environmental changes driven by the day-night cycle. This internal timekeeping mechanism is built on autoregulatory transcription-translation feedback loops that control the rhythmic expression of core clock genes and their protein products. The levels of clock proteins rise and ebb throughout a 24-h period through their rhythmic synthesis and destruction. In the ubiquitin-proteasome system, the process of polyubiquitination, or the covalent attachment of a ubiquitin chain, marks a protein for degradation by the 26S proteasome. The process is regulated by E3 ubiquitin ligases, which recognize specific substrates for ubiquitination. In this review, we summarize the roles that known E3 ubiquitin ligases play in the circadian clocks of two popular model organisms: mice and fruit flies. We also discuss emerging evidence that implicates the N-degron pathway, an alternative proteolytic system, in the regulation of circadian rhythms. We conclude the review with our perspectives on the potential for the proteolytic and non-proteolytic functions of E3 ubiquitin ligases within the circadian clock system.

In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, orchestrating behavioral and physiological rhythms in alignment to the environmental light/dark cycle. The neurons that comprise the SCN are anatomically and functionally heterogeneous, but despite their physiological importance, little is known about the pathways that guide their specification and differentiation. Here, we report that the stem/progenitor cell transcription factor, Sex determining region Y-box 2 ( Sox2 ), is required in the embryonic SCN to control the expression of SCN-enriched neuropeptides and transcription factors. Ablation of Sox2 in the developing SCN leads to downregulation of circadian neuropeptides as early as embryonic day (E) 15.5, followed by a decrease in the expression of two transcription factors involved in SCN development, Lhx1 and Six6 , in neonates. Thymidine analog-retention assays revealed that Sox2 deficiency contributed to reduced survival of SCN neurons during the postnatal period of cell clearance, but did not affect progenitor cell proliferation or SCN specification. Our results identify SOX2 as an essential transcription factor for the proper differentiation and survival of neurons within the developing SCN.

Various aspects of task execution load balancing of Internet of Things (IoTs) networks can be optimised using intelligent algorithms provided by software-defined networking (SDN). These load balancing aspects include makespan, energy consumption, and execution cost. While past studies have evaluated load balancing from one or two aspects, none has explored the possibility of simultaneously optimising all aspects, namely, reliability, energy, cost, and execution time. For the purposes of load balancing, implementing multi-objective optimisation (MOO) based on meta-heuristic searching algorithms requires assurances that the solution space will be thoroughly explored. Optimising load balancing provides not only decision makers with optimised solutions but a rich set of candidate solutions to choose from. Therefore, the purposes of this study were (1) to propose a joint mathematical formulation to solve load balancing challenges in cloud computing and (2) to propose two multi-objective particle swarm optimisation (MP) models; distance angle multi-objective particle swarm optimization (DAMP) and angle multi-objective particle swarm optimization (AMP). Unlike existing models that only use crowding distance as a criterion for solution selection, our MP models probabilistically combine both crowding distance and crowding angle. More specifically, we only selected solutions that had more than a 0.5 probability of higher crowding distance and higher angular distribution. In addition, binary variants of the approaches were generated based on transfer function, and they were denoted by binary DAMP (BDAMP) and binary AMP (BAMP). After using MOO mathematical functions to compare our models, BDAMP and BAMP, with state of the standard models, BMP, BDMP and BPSO, they were tested using the proposed load balancing model. Both tests proved that our DAMP and AMP models were far superior to the state of the art standard models, MP, crowding distance multi-objective particle swarm optimisation (DMP), and PSO. Therefore, this study enables the incorporation of meta-heuristic in the management layer of cloud networks.

Coronavirus disease 2019 (COVID-19) has emerged from China and globally affected the entire population through the human-to-human transmission of a newly emerged virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genome of SARS-CoV-2 encodes several proteins that are essential for multiplication and pathogenesis. The main protease (M pro or 3CL pro ) of SARS-CoV-2 plays a central role in its pathogenesis and thus is considered as an attractive drug target for the drug design and development of small-molecule inhibitors. We have employed an extensive structure-based high-throughput virtual screening to discover potential natural compounds from the ZINC database which could inhibit the M pro of SARS-CoV-2. Initially, the hits were selected on the basis of their physicochemical and drug-like properties. Subsequently, the PAINS filter, estimation of binding affinities using molecular docking, and interaction analyses were performed to find safe and potential inhibitors of SARS-CoV-2 M pro . We have identified ZINC02123811 (1-(3-(2,5,9-trimethyl-7-oxo-3-phenyl-7H-furo[3,2-g]chromen-6-yl)propanoyl)piperidine-4-carboxamide), a natural compound bearing appreciable affinity, efficiency, and specificity towards the binding pocket of SARS-CoV-2 M pro . The identified compound showed a set of drug-like properties and preferentially binds to the active site of SARS-CoV-2 M pro . All-atom molecular dynamics (MD) simulations were performed to evaluate the conformational dynamics, stability and interaction mechanism of M pro with ZINC02123811. MD simulation results indicated that M pro with ZINC02123811 forms a stable complex throughout the trajectory of 100 ns. These findings suggest that ZINC02123811 may be further exploited as a promising scaffold for the development of potential inhibitors of SARS-CoV-2 M pro to address COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)