Background: s/Aims: Endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy (LC) remains the most common therapeutic strategy used for cholecystocholedocholithiasis (CCL). Recently, single-stage ERCP + LC has gained popularity for treating CCL due to patient satisfaction and financial considerations. In this study, we aimed to compare the feasibility and efficacy of the two variants of single-stage ERCP + LC (starting with ERCP followed by LC versus starting with LC followed by ERCP) for treatment of CCL. Methods: A total of 115 patients who underwent single-stage ERCP + LC for CCL from January 2021 to December 2023 were enrolled in a retrospective comparative cohort study. These patients were divided into two groups: Group A (ERCP-first approach) and Group B (LC-first approach). Results: Patients in Group A had a common bile duct clearance rate of 88.2%, which was comparable to the 95.7% observed in Group B (p = 0.163). The mean duration of the ERCP procedure was comparable between the two groups (43.3 ± 11.8 vs 39.5 ± 13.5 minutes;p = 0.112). However, the mean duration of the LC procedure was significantly longer in Group A than in Group B (41.2 ± 8.98 vs 37.2 ± 12.2 minutes; p = 0.045). The mean total operative time for the combined ERCP + LC was significantly longer in Group A compared to Group B (81.9 ± 16.7 vs 75.1 ± 19.3 minutes; p = 0.046). Post-ERCP pancreatitis occurred in 4 patients in Group A and in 2 patients in Group B (p = 0.701). Conclusions Both LC-1st approach and ERCP-1st approach are feasible and highly effective for treating CCL through single-stage ERCP + LC. However, the LC-1st approach has the advantage of a shorter operative time.

Background: s/Aims: Endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy (LC) remains the most common therapeutic strategy used for cholecystocholedocholithiasis (CCL). Recently, single-stage ERCP + LC has gained popularity for treating CCL due to patient satisfaction and financial considerations. In this study, we aimed to compare the feasibility and efficacy of the two variants of single-stage ERCP + LC (starting with ERCP followed by LC versus starting with LC followed by ERCP) for treatment of CCL. Methods: A total of 115 patients who underwent single-stage ERCP + LC for CCL from January 2021 to December 2023 were enrolled in a retrospective comparative cohort study. These patients were divided into two groups: Group A (ERCP-first approach) and Group B (LC-first approach). Results: Patients in Group A had a common bile duct clearance rate of 88.2%, which was comparable to the 95.7% observed in Group B (p = 0.163). The mean duration of the ERCP procedure was comparable between the two groups (43.3 ± 11.8 vs 39.5 ± 13.5 minutes;p = 0.112). However, the mean duration of the LC procedure was significantly longer in Group A than in Group B (41.2 ± 8.98 vs 37.2 ± 12.2 minutes; p = 0.045). The mean total operative time for the combined ERCP + LC was significantly longer in Group A compared to Group B (81.9 ± 16.7 vs 75.1 ± 19.3 minutes; p = 0.046). Post-ERCP pancreatitis occurred in 4 patients in Group A and in 2 patients in Group B (p = 0.701). Conclusions Both LC-1st approach and ERCP-1st approach are feasible and highly effective for treating CCL through single-stage ERCP + LC. However, the LC-1st approach has the advantage of a shorter operative time.

Background: s/Aims: Endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy (LC) remains the most common therapeutic strategy used for cholecystocholedocholithiasis (CCL). Recently, single-stage ERCP + LC has gained popularity for treating CCL due to patient satisfaction and financial considerations. In this study, we aimed to compare the feasibility and efficacy of the two variants of single-stage ERCP + LC (starting with ERCP followed by LC versus starting with LC followed by ERCP) for treatment of CCL. Methods: A total of 115 patients who underwent single-stage ERCP + LC for CCL from January 2021 to December 2023 were enrolled in a retrospective comparative cohort study. These patients were divided into two groups: Group A (ERCP-first approach) and Group B (LC-first approach). Results: Patients in Group A had a common bile duct clearance rate of 88.2%, which was comparable to the 95.7% observed in Group B (p = 0.163). The mean duration of the ERCP procedure was comparable between the two groups (43.3 ± 11.8 vs 39.5 ± 13.5 minutes;p = 0.112). However, the mean duration of the LC procedure was significantly longer in Group A than in Group B (41.2 ± 8.98 vs 37.2 ± 12.2 minutes; p = 0.045). The mean total operative time for the combined ERCP + LC was significantly longer in Group A compared to Group B (81.9 ± 16.7 vs 75.1 ± 19.3 minutes; p = 0.046). Post-ERCP pancreatitis occurred in 4 patients in Group A and in 2 patients in Group B (p = 0.701). Conclusions Both LC-1st approach and ERCP-1st approach are feasible and highly effective for treating CCL through single-stage ERCP + LC. However, the LC-1st approach has the advantage of a shorter operative time.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Tamoxifen (TAM) is one of the most used drugs in the prevention and treatment of breast cancer. A set of common side effects was recorded associating its prolonged clinical use that ranges 3–10 years. This study aimed to investigate TAMinduced parietal cells (PCs) injury in rats and the possible protective effect of rhubarb (Rh) water extract (WE). Twentyfour adult female rats were distributed as: control group, TAM-group (3 mg/kg/day TAM for 4-weeks) and TAM+Rhgroup (combined 3 mg/kg/day TAM and 20 mg/kg Rh-WE for 4-weeks). Blood sample before euthanizing rats was tested for vitamin-B12. PCs in stomach fundus were examined using histological and transmission electron microscopic studies, besides immunohistochemistry for Caspase-3, proliferating cell nuclear antigen (PCNA) and hydrogen potassium (H + / K + )-ATPase. Gastric homogenates were inspected for malondialdehyde (MDA) by ELISA. TAM intake induced structural and ultrastructural alteration in rat PCs including ballooning degeneration, apoptosis, decreased canaliculi, increased tubulovesicular system and irregular-shaped mitochondria. A significant increase of Caspase-3 immunostaining and MDA expression in gastric tissue was associated with a significant decrease of PCNA and H + /K + -ATPase-immunostaining and in serum vitamin-B12 as compared to the control group. Combined oral intake of TAM and Rh-WE revealed a significant reversal of the previous findings. Conclusion: Prolonged use of oral TAM substantially affected the structure and function of gastric PCs which can be ameliorated by Rh-WE.

The terrible intensification in global food demand predictably results in an increase in agricultural practices, with a focus on the usage of herbicides. Hence, a deeper understanding of the impact of this herbicide on aquatic ecosystems is required. The characterization of nano-emulsion of fluazifop-P-butyl (FL) and the toxic effects in both traditional and nanoforms on the growth, pigmentation and ultrastructure of the freshwater microalgae: Auxenochlorella pyrenoidosa and Raphidocelis subcapitata were studied. The prepared nano-emulsion has a particle size of 52-94 nm by transmission electron microscopy (TEM). Zeta potential recorded (38.5 mV) and polydispersity index recorded (0.394). Traditional fluazifop-P-butyl (TFL) in the case of A. pyrenoidosa exhibited median effective concentration (EC50) (10.909 ± 3.635 mg/L) (P= 0.235), while nano fluazifop-P-butyl (NFL) recorded EC50 (14.281 ± 6.251 mg/L) (P= 0.205). In the case of R. subcapitata, TFL recorded EC50 (1.174 ± 0.501 mg/L) (P= 0.105), while NFL exhibited EC50 (4.757 ± 1.755 mg/L) (P= 0.150). Exposure of R. subcapitata cells to 0.117 mg/L of TFL significantly decreased chlorophyll a level by (-)15.51% (P= 0.002) relative to control. Also, chlorophyll b content in A. pyrenoidosa cells significantly decreased upon treatment with 1.43 mg/L of NFL by (-)67.16% (P= 0.001). Carotenoid content in A. pyrenoidosa cells significantly increased after exposure to 1.09 mg/L of TFL by 108.88% (P= 0.001) compared to the control. Likewise, exposure of R. subcapitata cells to 0.117 mg/L of TFL elevated carotenoid levels by 200.57% (P < 0.001). Destroyed chloroplasts and compacted cell walls were observed through TEM when A. pyrenoidosa was exposed to 1.09 mg/L of TFL and 1.43 mg/L of NFL. Likewise, R. subcapitata cells were exposed to 0.117 mg/L of TFL and 0.476 mg/L of NFL. This study demonstrates that both conventional and nano-forms of FL endanger the integrity of the ecosystem and have adverse impacts on non-target organisms. Thus, it's crucial to follow biosafety protocols concerning non-target species before deciding to use this herbicide.

Background: and Purpose Repetitive transcranial magnetic stimulation (rTMS) of the cerebellar hemisphere represents a new option in treating essential tremor (ET) patients. We aimed to determine the efficacy of cerebellar rTMS in treating ET using different protocols regarding the number of sessions, exposure duration, and follow-up duration. Methods: A randomized sham-controlled trial was conducted, in which 45 recruit patients were randomly allocated to 2 groups. The first (active group) comprised 23 patients who were exposed to 12 sessions of active rTMS with 900 pulses of 1-Hz rTMS at 90% of the resting motor threshold daily on each side of the cerebellar hemispheres over 4 weeks. The second group (sham group) comprised 22 patients who were exposed to 12 sessions of sham rTMS. Both groups were reassessed at baseline and after 1 day, 1 month, 2 months, and 3 months using the Fahn-Tolosa-Marin tremor-rating scale (FTM). Results: Demographic characteristics did no differ between the two groups. There were significant reductions both in FTM subscores A and B and in the FTM total score in the active-rTMS group during the period of assessment and after 3 months (p=0.031 and 0.011, respectively).However, subscore C did not change significantly from baseline when assessed at 2 and 3 months (p=0.073 and 0.236, respectively). Furthermore, the global assessment score was significantly higher in the active-rTMS group (p>0.001). Conclusions Low-frequency rTMS over the cerebellar cortex for 1 month showed relative safety and long-lasting efficacy in patients with ET. Further large-sample clinical trials are needed that include different sites of stimulation and longer follow-ups.